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NOZU Kandai
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Researcher basic information

■ Research news
  • 07 Aug. 2020, Alport Syndrome: Research highlights link between genotype and treatment effectiveness
    Link to Kobe Univ. HP
  • 03 Jul. 2020, Discovery of new disease-susceptibility gene for steroid-sensitive nephrotic syndrome
    Link to Kobe Univ. HP
  • 25 Jun. 2020, New treatment method for Alport Syndrome uses antisense oligonucleotides
    Link to Kobe Univ. HP
  • 26 Jul. 2018, Susceptible genes identified for childhood chronic kidney disease
    Link to Kobe Univ. HP
■ Research Keyword
  • Tubulopathies
  • Inherited Kidney Diseases
  • Pediatric Nephrology
  • Pediatrics
■ Research Areas
  • Life sciences / Fetal medicine/Pediatrics

Research activity information

■ Award
  • Oct. 2023 神戸大学, 神戸大学学長表彰（財務貢献）

  • Oct. 2022 神戸大学学長表彰（財務貢献）

  • Oct. 2021 神戸大学学長表彰（財務貢献）

  • Jun. 2021 Clinical and Experimental Nephrologyベストサイテーション賞

  • Apr. 2021 Pediatrics International Best Reviewer Award

  • Aug. 2020 神戸大学, 神戸大学学長表彰（財務貢献）

  • Aug. 2020 Japanese Society of Nephrology, Best presentation Award in JSN 63rd annual meeting, Alport症候群に対するエクソンスキッピング療法の開発

  • Apr. 2019 日本小児科学会, 2019年日本小児科学会学術研究賞, 遺伝性腎疾患における分子生物学的発症機序の解明および治療法の開発
    野津 寛大

  • May 2017 Japanese Society of Nephrology, The 1st Clinical Scientist Award, Alport症候群の臨床遺伝学的研究
    Kandai Nozu

  • Mar. 2017 川野小児医学奨学団体, 第17回小児医学川野賞, 小児遺伝性腎疾患における網羅的診断体制の確立および治療法の開発
    Nozu Kandai
    Others

  • May 2008 日本小児腎臓学会, The 43d Young Investigator's Award, 発端者のCOL4A5遺伝子に体細胞モザイクに変異を有し、軽症の臨床症状を示したAlport症候群の2家系
    Kandai Nozu

  • Jun. 2007 日本小児腎臓病学会, The 42th Young Investigator's Award, 日本人3型Bartter症候群患者5例における遺伝子型および表現型に関する研究
    Kandai Nozu

  • Jun. 2006 日本小児腎臓病学会, The 41st Young Investigator's Award, 尿中落下細胞の解析によりExon Skippingを証明できた1例
    Kandai Nozu

■ Paper
  • China Nagano, Naoya Morisada, Yuta Inoki, Yu Tanaka, Yuta Ichikawa, Chika Ueda, Hideaki Kitakado, Yuya Aoto, Nana Sakakibara, Tomoko Horinouchi, Tomohiko Yamamura, Shingo Ishimori, Kandai Nozu
    BACKGROUND: Autosomal-dominant tubulointerstitial kidney disease caused by MUC1 (ADTKD-MUC1) is a rare disorder characterized by progressive kidney dysfunction. Pathogenic variants in MUC1 are difficult to detect owing to the variable number tandem repeat region. To address this issue, VNtyper-Kestrel, a bioinformatics pipeline for short-read sequencing data, was recently developed. In this study, the performance of VNtyper-Kestrel for detecting MUC1 variants in clinical settings was evaluated. METHODS: We used VNtyper-Kestrel to retrospectively analyze short-read sequencing data for 209 individuals with suspected ADTKD who were previously evaluated through long-read sequencing. Data from a panel including ~ 180 genes and an ADTKD-specific panel were used. In addition, the pipeline was applied to 976 patients with suspected hereditary kidney diseases other than ADTKD and positive cases were validated using long-read sequencing. Accuracy was assessed by comparisons with the results of long-read sequencing. RESULTS: Using VNtyper-Kestrel, we identified MUC1 variants in 16 of 19 confirmed cases of ADTKD-MUC1. Three initially negative cases were reanalyzed using the ADTKD-specific panel, yielding positive detection results with high confidence. We obtained two low-confidence positive results from 190 cases of suspected ADTKD and 10 low-confidence positive results among 976 non-ADTKD cases; however, all were classified as false positives upon long-read sequencing validation. CONCLUSIONS: VNtyper-Kestrel demonstrated high sensitivity in identifying MUC1 variants when sequencing coverage was adequate, supporting its potential as a rapid and cost-effective screening tool. However, confirmatory long-read sequencing is needed in uncertain cases. Optimizing coverage and refining patient selection criteria could improve the clinical utility of this approach.
    Apr. 2025, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal

  • Yu Tanaka, Tomoko Horinouchi, Yuta Inoki, Yuta Ichikawa, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, Shingo Ishimori, Tomohiko Yamamura, China Nagano, Kandai Nozu
    BACKGROUND: Isotonic fluids are becoming the standard for hydration and maintenance fluid therapy, but there is no consensus on the optional choice among the different types of isotonic solution. METHODS: This study is a single-center, non-randomized controlled trial at Kobe University Hospital, Japan, between April 2021 and March 2023. The study included pediatric patients aged 1-19 years who underwent kidney biopsies. From April 2021 to March 2022, 0.9% sodium chloride (saline) was administered, and from April 2022 to March 2023, balanced crystalloids were used. The primary outcome was the occurrence of hyponatremia (< 137 mEq/L) after a kidney biopsy. Secondary outcomes included other electrolyte balances, blood gas parameters, creatinine-based estimated glomerular filtration rate (Cr-eGFR), and arginine vasopressin concentrations (UMIN Clinical Trial Registry: UMIN 000044330). RESULTS: Of 61 patients enrolled, 2 were excluded, leaving 34 in the saline group and 25 in the balanced crystalloid group. No hyponatremia occurred, and serum sodium concentrations were similar between both groups (138.7 vs. 138.9 mEq/L, P = 0.08). The saline group showed a greater increase in serum chloride (+ 1.7 vs. + 0.2, P < 0.01) and a greater decrease in HCO3- concentrations (- 0.6 vs. + 0.9, P < 0.01). There were minimal changes in pH (- 0.01 vs. - 0.01, P = 0.99) and Cr-eGFR (- 1.5 vs. + 1.1 mL/min/1.73 m2, P = 0.96) in both groups. CONCLUSIONS: During pediatric kidney biopsy, both saline and balanced crystalloids were effective in preventing hyponatremia. Although saline infusion results in higher serum chloride concentrations and lower blood HCO3- concentrations than balanced crystalloids infusion, the clinical significance was minimal.
    Apr. 2025, Pediatric nephrology (Berlin, Germany), 40(4) (4), 1033 - 1040, English, International magazine
    Scientific journal

  • Yuta Inoki, Tomoko Horinouchi, Shuhei Aoyama, Yuka Kimura, Yuta Ichikawa, Yu Tanaka, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, Koichi Kamei, Riku Hamada, Naoya Fujita, Yoshimitsu Gotoh, Yoshitsugu Kaku, Kei Nishiyama, Takayuki Okamoto, Yukiko Toya, Tomohiko Yamamura, Shingo Ishimori, China Nagano, Kandai Nozu
    BACKGROUND: More than half of patients with congenital nephrotic syndrome (CNS) or infantile nephrotic syndrome (infantile NS) have a monogenic aetiology. This study aimed to clarify differences in the clinical course, genetic background, and genotype-phenotype correlation between CNS and infantile NS. METHODS: We enrolled patients who were diagnosed with CNS or infantile NS and referred to our hospital for genetic analysis and investigated the clinical characteristics and genetic background of patients with identified causative genes. RESULTS: Among 74 patients enrolled, disease-causing genetic variants were detected in 50 patients. The median age for developing kidney failure in the genetic CNS (n = 33) and genetic infantile NS (n = 17) groups with monogenic variants was 13.2 and 19.0 months, respectively (P = 0.13). The age at developing kidney failure was significantly earlier in CNS patients with genes other than NPHS1 than in CNS patients with NPHS1 variants (1.0 vs. 31.0 months; P < 0.001). In patients with pathogenic variants other than NPHS1, there was a significant difference in the age at developing kidney failure between CNS and infantile NS patients (1.0 vs. 15.0 months; P < 0.001). Of patients with NPHS1 variants, no infants with NS had any truncating variants or developed kidney failure during follow-up. CONCLUSIONS: The onset of CNS or infantile NS affects the kidney prognosis in patients with genetic nephrotic syndrome. Among patients with pathogenic variants in the same gene, patients with infantile NS may have a milder genotype and better prognosis than those with CNS.
    Mar. 2025, Pediatric nephrology (Berlin, Germany), English, International magazine
    Scientific journal

  • Tomoko Horinouchi, Kandai Nozu, Kazumoto Iijima
    Nephrotic syndrome is the most common glomerular disease in children, and various hypotheses regarding its etiology have been proposed, primarily focusing on immune-related mechanisms. Nephrotic syndrome can manifest as a monogenic disease caused by deleterious variants in genes such as NPHS1, which encodes nephrin. In steroid-sensitive nephrotic syndrome, HLA class II and immune-related genes have been identified as susceptibility genes. Moreover, NPHS1 is a susceptibility gene for steroid-sensitive nephrotic syndrome in patients from East Asian populations. Anti-nephrin antibodies have been identified as a significant factor in the pathogenesis of nephrotic syndrome. These discoveries have substantially advanced our understanding of nephrotic syndrome. However, the mechanisms underlying the production of anti-nephrin antibodies and their association with genetic backgrounds have remained unclear and warrant further investigation.
    Mar. 2025, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal

  • Yu Tanaka, China Nagano, Nana Sakakibara, Eri Okada, Shuhei Aoyama, Yuka Kimura, Yuta Inoki, Yuta Ichikawa, Chika Ueda, Hideaki Kitakado, Tomoko Horinouchi, Tomohiko Yamamura, Shingo Ishimori, Kazumoto Iijima, Kandai Nozu, Naoya Morisada
    BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by tubular atrophy, interstitial fibrosis, and progressive kidney dysfunction. Its causative genes include UMOD, MUC1, REN, HNF1B, and SEC61A1. ADTKD contributes to unexplained chronic kidney disease (CKD), and many cases remain genetically undiagnosed. This study aimed to elucidate the clinical features of patients genetically diagnosed with ADTKD in Japan. METHODS: We included individuals with suspected congenital anomalies of the kidney and urinary tract, nephronophthisis, polycystic kidney disease, or ADTKD. Genetic analyses using direct sequencing, short-read next-generation sequencing (SRS), and/or long-read next-generation sequencing (LRS) were performed on 1097 families. Patients with ADTKD-HNF1B were excluded due to prior reporting. RESULTS: Variants in UMOD, MUC1, REN, and SEC61A1 were identified in 52 patients from 40 families (18, 16, 5, and 1 family, respectively). The median age at diagnosis was 38.5 years, and the urinary protein-to-creatinine ratio was 0.05 g/gCr. End-stage kidney disease was present at diagnosis in 37% of patients. Genetic testing was performed in 58% due to suspected ADTKD based on pathology or clinical course and in 38% due to unexplained CKD. Kidney biopsies were performed in 55%, with ADTKD confirmed pathologically in 41%. SRS and LRS were used in 55% and 30% of all families, respectively; for ADTKD-MUC1, 75% of families were analyzed using LRS. CONCLUSIONS: Clinical and pathological diagnosis of ADTKD remains challenging, emphasizing the importance of comprehensive genetic testing. Enhanced access to advanced genetic testing such as LRS is essential to improve diagnostic precision and management.
    Feb. 2025, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal

  • Takashi Uechi, Tomoko Horinouchi, Yuta Inoki, Yu Tanaka, Hideaki Kitakado, Chika Ueda, China Nagano, Masato Yamaguchi, Yoriko Tsuji, Kandai Nozu
    Systemic lupus erythematosus (SLE) can present with various symptoms, including rare manifestations such as gangrene. This report describes a 12-year-old girl with SLE who presented with intermittent claudication and gangrene. Although intermittent claudication is rare in paediatric cases, it is essential to consider vascular diseases including those associated with SLE as a potential cause. The patient initially experienced pain, redness, and cold sensations in the right great toe accompanied by intermittent claudication, with symptoms worsening over time. Diagnostic imaging, including contrast-enhanced CT and MRI, revealed occlusion of the right popliteal artery with associated vasculitis and thrombosis. The diagnosis of SLE and antiphospholipid syndrome was confirmed based on clinical criteria. Treatment included prednisone, methylprednisolone pulse therapy, mycophenolate mofetil, hydroxychloroquine, and anticoagulants. The patient showed significant improvement, with resolution of the claudication and effective management of her gangrene through immunosuppressive therapy and careful wound care. This case highlights the importance of considering vascular complications in paediatric SLE and underscores the need for early diagnosis and comprehensive treatment.
    Feb. 2025, Modern rheumatology case reports, English, International magazine
    Scientific journal

  • Sungwon Hong, Kiiko Iketani, Shoko Sonehara, Hiroaki Hanafusa, Yoshinori Nambu, Kandai Nozu, Hiroyuki Awano, Ryosuke Bo
    The coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide, and pediatric patients with underlying diseases are at high risk of developing severe COVID-19. However, there are limited reports on the clinical impact of COVID-19, especially in patients with underlying neuromuscular diseases (NMD) and inborn errors of metabolism (IEM). This study aimed to investigate the incidence and clinical presentation of COVID-19 in patients with NMD and IEM. This was a single-center, cross-sectional study of patients with NMD and IEM in Japan for 2 years, from April 1, 2020 to March 31, 2022. Among 255 participants with a median age of 14 (range: 0-50) years, 192 (75%) and 63 (25%) had NMD and IEM, respectively. Among 255 patients, 8 (5 NMD and 3 IEM) were positive for the anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody, and the incidence was considered 3%. All positive patients had mild or asymptomatic COVID-19. None of the patients exhibited moderate or severe symptoms. In conclusion, this study revealed that the incidence of COVID-19 was low, and mild or subclinical infection was common even in patients with NMD and IEM, who may be at a higher risk of severe COVID-19.
    Feb. 2025, The Kobe journal of medical sciences, 70(4) (4), E106-E112, English, Domestic magazine
    Scientific journal

  • Hideaki Kitakado, Tomoko Horinouchi, Shuhei Aoyama, Yuka Kimura, Yuta Inoki, Yu Tanaka, Chika Ueda, Yuya Aoto, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Shingo Ishimori, Rini Rossanti, Masafumi Matsuo, Kandai Nozu
    INTRODUCTION: Alport syndrome (AS) is an inherited kidney disease caused by variants in the COL4A3, COL4A4, or COL4A5 genes, resulting in type IV collagen abnormalities. Although autosomal dominant variants in COL4A3 and COL4A4 are increasingly being diagnosed, X-linked AS (XLAS) caused by COL4A5 variants predominates. Single nucleotide substitutions in introns positioned at first and second from the last nucleotide (called a consensus sequence) of exons always cause aberrant splicing. However, whether intronic variants at the third to fifth positions from the last nucleotide of exons can cause aberrant splicing is unclear. METHODS: We identified 11 intronic variants positioned at the third, fourth, and fifth nucleotides from the exon 3' end in COL4A5 from our AS cohort (January 2006-July 2022). We conducted in vitro splicing assays using minigenes and in silico splicing analysis using commercial splicing prediction software and evaluated mRNA sequences obtained from patients' samples when available. RESULTS: All 11 patients showed aberrant splicing patterns in the minigene splicing assays. In vivo analysis of 6 patients corroborated these findings. The commercial splicing prediction software accurately predicted splicing changes in 10 variants. CONCLUSIONS: This study shows that 11 intronic variants at the third to fifth positions in COL4A5 introns cause aberrant splicing. This finding highlights the importance of evaluating such variants for the diagnosis and prognosis of XLAS. Further investigation is warranted to confirm the pathogenicity of these variants and their effect on the prognosis of the kidney in XLAS.
    Feb. 2025, Kidney international reports, 10(2) (2), 516 - 521, English, International magazine
    Scientific journal

  • Toshiyuki Imasawa, Kei Murayama, Daishi Hirano, Kandai Nozu
    Springer Science and Business Media LLC, Dec. 2024, Clinical and Experimental Nephrology, 29(1) (1), 39 - 56
    Scientific journal

  • Kensuke Yabuuchi, Tomoko Horinouchi, Tomohiko Yamamura, Kandai Nozu, Minoru Takasato
    Alport syndrome (AS) is a hereditary disease caused by mutations in the COL4A5 gene and leads to chronic kidney disease. Currently, no specific treatment has been developed. However, a recent study using AS-model mice demonstrated that the exon skipping method could partially rescue the symptoms. In this study, we evaluated the effects of the exon skipping method using kidney organoids generated from AS-patient-derived induced pluripotent stem cells (AS-iPSCs). We generated kidney organoids from AS-iPSCs, which exhibited nephron structures. As expected, the C-terminus of COL4A5 was not expressed in AS-organoids. Interestingly, anti-sense oligonucleotides restored the expression of the C-terminus of COL4A5 in vitro. Next, we transplanted AS-organoids into mice and evaluated glomerular basement membrane formation in vivo. We found that AS-organoids formed a lower slit diaphragm ratio compared to control organoids. Finally, we assessed the effects of exon skipping on transplanted organoids but observed minimum effects. These studies suggest that AS-iPSCs can generate kidney organoids lacking the C-terminus of COL4A5, and that exon skipping can induce its expression in vitro.
    Dec. 2024, Genes to cells : devoted to molecular & cellular mechanisms, 29(12) (12), 1118 - 1130, English, International magazine
    Scientific journal

  • Shizuka Oikawa, Hiroshi Yamaguchi, Masahiro Nishiyama, Tatsuhito Ito, Aoi Kawamura, Tomohiro Sameshima, Kento Soma, Takuya Ueda, Shoichi Tokumoto, Yusuke Ishida, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Hiroaki Nagase
    OBJECTIVE: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.
    Nov. 2024, Journal of the neurological sciences, 466, 123238 - 123238, English, International magazine
    Scientific journal

  • RAS阻害薬不応の蛋白尿を呈し遺伝学的検査でCUBN異常症と診断した1例
    相原 久人, 仲川 真由, 遠藤 周, 安部 信平, 鈴木 光幸, 野津 寛大, 清水 俊明
    (公社)日本小児科学会, Nov. 2024, 日本小児科学会雑誌, 128(11) (11), 1478 - 1478, Japanese

  • Takuya Ueda, Masahiro Nishiyama, Hiroshi Yamaguchi, Kento Soma, Yusuke Ishida, Azusa Maruyama, Kandai Nozu, Hiroaki Nagase
    INTRODUCTION: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice. METHODS: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023. RESULTS: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age. CONCLUSIONS: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone.
    Nov. 2024, Brain & development, 46(10) (10), 332 - 338, English, International magazine
    Scientific journal

  • Yuta Inoki, Tomoko Horinouchi, Tomohiko Yamamura, Shingo Ishimori, Yuta Ichikawa, Yu Tanaka, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, China Nagano, Kandai Nozu
    KEY POINTS: Patients with both COL4A3 and COL4A4 variants exhibited poor renal prognosis compared with those with autosomal dominant Alport syndrome. The proportion of patients with digenic Alport syndrome was 1.7% among all patients with Alport syndrome. BACKGROUND: Digenic Alport syndrome could be associated with poor renal prognosis. However, the characteristics of patients with digenic Alport syndrome remain ambiguous. METHODS: We retrospectively investigated the clinical symptoms, pathological findings, genetic variants, and proportions of patients with digenic Alport syndrome. The ages at detection of proteinuria and development of ESKD were compared between patients with digenic Alport syndrome with disease-causing variants in COL4A3 and COL4A4 and those with autosomal dominant Alport syndrome (ADAS) previously analyzed by our group. RESULTS: Eighteen patients from nine families with digenic variants in COL4A3 and COL4A4 and four male and five female patients with digenic variants in COL4A5 and COL4A3 or COL4A4 were enrolled in this study. Next-generation sequencing revealed that the proportion of patients with digenic Alport syndrome was 1.7% among all patients with Alport syndrome. In patients with digenic variants in COL4A3 and COL4A4, the median ages at detection of proteinuria and ESKD were 10.0 and 57.0 years, respectively. Compared with the patients with ADAS, the age at detection of proteinuria tended to be earlier (10.0 versus 20.0 years; P = 0.073) and that at development of ESKD was significantly earlier (57.0 versus 72.0 years; P = 0.045) in patients with digenic Alport syndrome. CONCLUSIONS: Overall, patients with digenic Alport syndrome harboring COL4A3 and COL4A4 variants exhibited poor renal compared with the patients with ADAS. Therefore, timely identification of the two disease-causing variants is critical for the renal prognostic assessment and early treatment of patients with digenic Alport syndrome.
    Oct. 2024, Kidney360, 5(10) (10), 1510 - 1517, English, International magazine
    Scientific journal

  • Ryota Suzuki, Nana Sakakibara, Sae Murakami, Yuta Ichikawa, Hideaki Kitakado, Chika Ueda, Yu Tanaka, Eri Okada, Atsushi Kondo, Yuya Aoto, Shinya Ishiko, Shingo Ishimori, China Nagano, Tomohiko Yamamura, Tomoko Horinouchi, Takayuki Okamoto, Kandai Nozu
    BACKGROUND AND HYPOTHESIS: Male patients with X-linked Alport syndrome (XLAS) generally develop end-stage kidney disease in early or middle adulthood and show distinct genotype-phenotype correlations. Female patients, however, show various phenotypes ranging from asymptomatic to severe with no genotype-phenotype correlations. However, the factors affecting the severity of XLAS in female patients are unclear. Since X-chromosome inactivation (XCI) affects the severity of certain female X-linked diseases, we investigated whether genotype and XCI were associated with XLAS severity in female patients in a large Japanese cohort. METHODS: Among 139 female patients with genetically diagnosed XLAS at our institution, we conducted XCI analysis on peripheral blood leukocytes using the human androgen receptor assay method and analyzed two cohorts. In 74 adult female patients, we evaluated the correlation between kidney function (creatinine-estimated glomerular filtration rate [Cr-eGFR] optimized for Japanese individuals) and genotype/XCI using multivariable linear regression analysis, and in 65 pediatric female patients, we evaluated the correlation between kidney function (Cr-eGFR optimized for Japanese individuals) and genotype/XCI using multivariable linear regression analysis. We also investigated the correlation between the development of proteinuria (urine protein-to-creatinine ratio above normal for the patient's age) and genotype/XCI using multivariable Cox proportional hazard analysis. RESULTS: In adult female patients, XCI pattern was significantly associated with Cr-eGFR (regression coefficient estimate = -0.53, P = 0.004), whereas genotype was not (P = 0.892). In pediatric female patients, both genotype and XCI pattern were significant independent risk factors for the development of proteinuria (hazard ratio [HR], 3.702; 95% confidence interval [CI], 1.681-8.150; P = 0.001 and HR, 1.043; 95% CI, 1.061-1.070; P = 0.001, respectively), whereas both genotype and XCI pattern were not associated with Cr-eGFR (P = 0.20, P = 0.67, respectively). CONCLUSION: Genotype and XCI are factors associated with the severity in females with XLAS.
    Aug. 2024, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, English, International magazine
    Scientific journal

  • 曽根原 晶子, 大橋 浩基, 松井 美樹, 花房 宏昭, 南部 静紀, 李 知子, 粟野 宏之, 竹島 泰弘, 野津 寛大, 坊 亮輔
    (一社)日本マススクリーニング学会, Jul. 2024, 日本マス・スクリーニング学会誌, 34(2) (2), 209 - 209, Japanese

  • 本邦のネフローゼ患者における抗ネフリン抗体の発現について
    長野 智那, 市川 裕太, 堀之内 智子, 藤井 秀毅, 飯島 一誠, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 568 - 568, Japanese

  • 原因除去後長期にわたり維持する偽性Gitelman症候群の検討
    近藤 淳, 猪野木 雄太, 市川 裕太, 田中 悠, 上田 知佳, 北角 英昌, 榊原 菜々, 長野 智那, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 574 - 574, Japanese

  • 遺伝学的に診断された常染色体顕性尿細管間質性腎疾患の臨床像
    田中 悠, 森貞 直哉, 岡田 絵里, 長岡 由修, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 574 - 574, Japanese

  • Alport症候群患者の診断における3歳児検尿の役割の検討
    北角 英晶, 猪野木 雄太, 市川 裕太, 田中 悠, 上田 知佳, 近藤 淳, 榊原 菜々, 長野 智那, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 576 - 576, Japanese

  • Digenic Alport syndromeの重症度に関する検討
    猪野木 雄太, 堀之内 智子, 田中 悠, 市川 裕太, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 長野 智那, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 576 - 576, Japanese

  • 腎生検時輸液における生理食塩水とリンゲル液の安全性の比較に関する検討
    田中 悠, 堀之内 智子, 猪野木 雄太, 市川 裕太, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 長野 智那, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 577 - 577, Japanese

  • 免疫抑制薬未使用の小児頻回再発型/ステロイド依存性ネフローゼ症候群に対するリツキシマブ医師主導治験
    飯島 一誠, 佐古 まゆみ, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 578 - 578, Japanese

  • ネフリン/IgGカクテル抗体を用いた小児特発性ネフローゼ症候群腎組織の抗ネフリン抗体検出とその有用性
    市川 裕太, 榊原 菜々, 猪野木 雄太, 田中 悠, 上田 知佳, 北角 英晶, 近藤 淳, 長野 智那, 堀之内 智子, 丸山 順裕, 飯島 一誠, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 579 - 579, Japanese

  • 早産や低出生体重児の潜在的レニン・アンギオテンシン・アルドステロン(RAAS)系亢進の存在に関する検討
    石森 真吾, 北角 英晶, 近藤 淳, 藤村 順也, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 598 - 598, Japanese

  • OCRL異常症の表現型は,phosphatidylinositol 4,5-bisphosphate 5-phosphatase活性と相関する
    鈴木 諒太, 榊原 菜々, 市川 裕太, 北角 英晶, 上田 知佳, 田中 悠, 岡田 絵里, 近藤 淳, 長野 智那, 堀之内 智子, 岡本 孝之, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 599 - 599, Japanese

  • 検尿異常により発見された蛋白尿症と単一遺伝子異常との関連
    榊原 菜々, 猪野木 雄太, 市川 裕太, 田中 悠, 北角 英晶, 上田 知佳, 近藤 淳, 長野 智那, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Jun. 2024, 日本腎臓学会誌, 66(4) (4), 676 - 676, Japanese

  • 稲熊 洋祐, 貝藤 裕史, 矢谷 和也, 森貞 直哉, 吉田 牧子, 野津 寛大, 中西 浩一, 田中 亮二郎, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2024, 日本小児腎臓病学会雑誌, 37(Suppl.) (Suppl.), 111 - 111, Japanese

  • 川村 葵, 西山 将広, 伊藤 立人, 京野 由紀, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 山口 宏, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S206 - S206, Japanese

  • 山口 宏, 伊藤 立人, 相馬 健人, 川村 葵, 鮫島 智大, 京野 由紀, 上田 拓耶, 老川 静香, 徳元 翔一, 石田 悠介, 西山 将広, 丸山 あずさ, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S225 - S225, Japanese

  • 老川 静香, 山口 宏, 伊藤 立人, 相馬 建人, 川村 葵, 上田 拓郎, 鮫島 智大, 京野 由紀, 徳元 翔一, 石田 悠介, 西山 将広, 丸山 あずさ, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S225 - S225, Japanese

  • Hiroyuki Awano, Yoshinori Nambu, Chieko Itoh, Akihiro Kida, Tetsushi Yamamoto, Tomoko Lee, Yasuhiro Takeshima, Kandai Nozu, Masafumi Matsuo
    INTRODUCTION/AIMS: Duchenne muscular dystrophy (DMD) presents with skeletal muscle weakness, followed by cardiorespiratory involvement. The need for longitudinal data regarding DMD that could serve as a control for determining treatment efficacy in clinical trials has increased notably. The present study examined the longitudinal data of Japanese DMD patients collectively and assessed individual patients with pathogenic variants eligible for exon-skipping therapy. METHODS: Patients with DMD who visited Kobe University Hospital between March 1991 and March 2019 were enrolled. Data between the patients' first visit until age 20 years were examined. RESULTS: Three hundred thirty-seven patients were included. Serum creatine kinase levels showed extremely high values until the age of 6 years and a rapid decline from ages 7-12 years. Both the median 10-m run/walk velocity and rise-from-floor velocity peaked at the age of 4 years and declined with age. The values for respiratory function declined from the age of 11 years. The median left ventricular ejection fraction was >60% until the age of 12 years and rapidly declined from ages 13-15 years. Examination of the relationship between pathogenic variants eligible for exon-skipping therapy and longitudinal data revealed no characteristic findings. DISCUSSION: We found that creatine kinase levels and motor, respiratory, and cardiac functions each exhibited various changes over time. These findings provide useful information about the longitudinal data of several outcome measures for patients with DMD not receiving corticosteroids. These data may serve as historical controls in comparing the natural history of DMD patients not on regular steroid use in appropriate clinical trials.
    May 2024, Muscle & nerve, 69(5) (5), 604 - 612, English, International magazine
    Scientific journal

  • Chika Ueda, Tomoko Horinouchi, Yuta Inoki, Yuta Ichikawa, Yu Tanaka, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Junya Fujimura, Naohiro Kamiyoshi, Shingo Ishimori, Takeshi Ninchoji, Hiroshi Kaito, Yuko Shima, Kazumoto Iijima, Kandai Nozu, Norishige Yoshikawa
    BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses. METHODS: In this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients. RESULTS: Out of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5-8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up. CONCLUSIONS: Most patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis.
    Apr. 2024, Pediatric nephrology (Berlin, Germany), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yuimi Koyama, Mary Ann Suico, Aimi Owaki, Ryoichi Sato, Jun Kuwazuru, Shota Kaseda, Yuya Sannomiya, Jun Horizono, Kohei Omachi, Tomoko Horinouchi, Tomohiko Yamamura, Haruki Tsuhako, Kandai Nozu, Tsuyoshi Shuto, Hirofumi Kai
    Springer Science and Business Media LLC, Apr. 2024, Clinical and Experimental Nephrology
    Scientific journal

  • Yu Tanaka, Tomoko Horinouchi, Yuta Inoki, Yuta Ichikawa, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, China Nagano, Yoshihiko Yano, Norishige Yoshikawa, Naoya Morisada, Kandai Nozu
    We present a case of nephronophthisis 13 that resulted from WDR19 variants. The patient, a nine-year-old Japanese boy, had detection of mild proteinuria during a school urine screening. Urinalysis revealed mild proteinuria without hematuria. Blood tests indicated pancytopenia, mild elevation of liver enzymes, and kidney dysfunction. Ultrasound examination disclosed hepatosplenomegaly. Abdominal computed tomography and bone marrow assessments ruled out malignant tumors. Subsequent kidney and liver biopsies suggested nephronophthisis and congenital hepatic fibrosis. Furthermore, comprehensive genetic analysis through next-generation sequencing revealed compound heterozygous variants in WDR19 (NM_025132.4), including the previously reported c.3533G > A, p.(Arg1178Gln), and c.3703G > A, p.(Glu1235Lys) variants, confirming the diagnosis of nephronophthisis 13. There is potential need for liver and kidney transplantation in patients with nephronophthisis and hepatic fibrosis. Early diagnosis is therefore crucial to mitigate delays in treating complications associated with kidney and hepatic insufficiency and to facilitate preparation of transplantation. To achieve early diagnosis of nephronophthisis, it is imperative to consider it as a differential diagnosis when extrarenal symptoms and kidney dysfunction coexist, particularly when mild proteinuria is observed through opportunistic urinalysis. Genetic testing is important because nephronophthisis manifests as diverse symptoms, necessitating an accurate diagnosis. Next-generation sequencing was shown to be invaluable for the genetic diagnosis of nephronophthisis, given the numerous identified causative genes.
    Apr. 2024, CEN case reports, English, Domestic magazine
    Scientific journal

  • 膵仮性嚢胞内の仮性動脈瘤破裂を来した重症心身障がい児の1例
    亀岡 泰幸, 鮫島 由友, 大片 祐一, 高成田 祐希, 口分田 啓, 岩渕 瀬怜奈, 冨岡 雄一郎, 中井 優美子, 坊 亮輔, 堀之内 智子, 岡田 卓也, 阪口 博哉, 阿部 洋文, 小林 隆, 野津 寛大, 尾藤 祐子
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 631, Japanese

  • 国産手術支援ロボットhinotoriによるロボット支援下左副腎褐色細胞腫摘出術を行った1例
    大片 祐一, 古川 順也, 坊 亮輔, 口分田 啓, 亀岡 泰幸, 岩渕 瀬怜奈, 高成田 祐希, 冨岡 雄一郎, 鮫島 由友, 中井 優美子, 山本 暢之, 中野 雄造, 野津 寛大, 尾藤 祐子
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 632, Japanese

  • 3歳時の就寝時刻が遅いと小学1年生時の勤勉性や思いやりが低下する 尼崎市コホート研究
    西山 将広, 京野 由紀, 川村 葵, 老川 静香, 徳元 翔一, 山口 宏, 冨岡 和美, 野津 寛大, 永瀬 裕朗
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 625 - 625, Japanese

  • 不全型川崎病に続発した全身型若年性特発性関節炎の1例
    相馬 健人, 堀之内 智子, 合田 由香利, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 真鍋 修司, 佐野 浩子, 南川 将吾, 中岸 保夫, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 619 - 620, Japanese

  • 潰瘍性大腸炎の発症時に免疫性血小板減少症を合併した1例
    今川 幸人, 堀之内 智子, 近藤 淳, 岡本 典大, 宮崎 はる香, 田中 悠, 市川 裕太, 上田 知佳, 北角 英晶, 田村 彰広, 渡邉 大輔, 山本 暢之, 榊原 菜々, 大井 充, 星 奈美子, 児玉 祐三, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 624 - 624, Japanese

  • 小児SLEに対してアニフロルマブを使用した2例
    国本 一輝, 堀之内 智子, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 625 - 625, Japanese

  • 抗TNFα抗体製剤使用中に乾癬様皮疹が出現した2例
    高橋 慧, 堀之内 智子, 近藤 淳, 岡本 典大, 宮崎 はる香, 徳永 英里, 猪野木 雄太, 田中 悠, 北角 英晶, 渡邉 大輔, 大井 充, 児玉 裕三, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 630 - 631, Japanese

  • 生後1週以降の頻脈で発症したMMI内服中のバセドウ病母体から出生した新生児バセドウ病の1例
    松澤 実法, 鮫島 智大, 岡田 怜, 加古 優香, 福田 拓弥, 阿部 真也, 芦名 満理子, 坊 亮輔, 粟野 宏之, 藤岡 一路, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 616 - 616, Japanese

  • 卵巣ステロイド細胞腫瘍合併母体から出生した46,XX性分化異常症の児
    岡田 怜, 加古 優香, 福田 拓弥, 鮫島 智大, 城戸 拓海, 阿部 真也, 芦名 満理子, 藤岡 一路, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 617 - 617, Japanese

  • 全身合併症を伴った前眼部形成異常の1例
    加古 優香, 阿部 真也, 岡田 怜, 福田 拓弥, 鮫島 智大, 城戸 拓海, 芦名 満理子, 藤岡 一路, 野津 寛大
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 617 - 618, Japanese

  • 膵仮性嚢胞内の仮性動脈瘤破裂を来した重症心身障がい児の1例
    亀岡 泰幸, 鮫島 由友, 大片 祐一, 高成田 祐希, 口分田 啓, 岩渕 瀬怜奈, 冨岡 雄一郎, 中井 優美子, 坊 亮輔, 堀之内 智子, 岡田 卓也, 阪口 博哉, 阿部 洋文, 小林 隆, 野津 寛大, 尾藤 祐子
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 631, Japanese

  • 国産手術支援ロボットhinotoriによるロボット支援下左副腎褐色細胞腫摘出術を行った1例
    大片 祐一, 古川 順也, 坊 亮輔, 口分田 啓, 亀岡 泰幸, 岩渕 瀬怜奈, 高成田 祐希, 冨岡 雄一郎, 鮫島 由友, 中井 優美子, 山本 暢之, 中野 雄造, 野津 寛大, 尾藤 祐子
    (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 631 - 632, Japanese

  • Hiroaki Hanafusa, Hiroshi Yamaguchi, Naoya Morisada, Ming Juan Ye, Riki Matsumoto, Hiroaki Nagase, Kandai Nozu
    Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.
    Mar. 2024, Human genome variation, 11(1) (1), 17 - 17, English, International magazine
    Scientific journal

  • Naoko Nakatani, Akihiro Tamura, Hiroaki Hanafusa, Nanako Nino, Nobuyuki Yamamoto, Hiroyuki Awano, Yasuhiro Tanaka, Naoya Morisada, Suguru Uemura, Atsuro Saito, Daiichiro Hasegawa, Kandai Nozu, Yoshiyuki Kosaka
    Recently, heterozygous loss-of-function NFKB1 variants were identified as the primary cause of common variable immunodeficiency (CVID) in the European population. However, pathogenic NFKB1 variants have never been reported in the Japanese population. We present a 29-year-old Japanese woman with CVID. A novel variant, c.136 C > T, p.(Gln46*), was identified in NFKB1. Her mother and daughter carried the same variant, demonstrating the first Japanese pedigree with an NFKB1 pathogenic variant.
    Mar. 2024, Human genome variation, 11(1) (1), 15 - 15, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshiki Hyodo, Shigeo Hara, Shunsuke Goto, Hideki Fujii, Shinichi Nishi, Tomoko Horinouchi, Kandai Nozu, Norishige Yoshikawa, Akihiro Yoshimoto, Tomoo Itoh
    PURPOSE: Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis. METHODS: The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry. RESULTS: IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group. CONCLUSION: The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.
    Feb. 2024, International urology and nephrology, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yuki Kyono, Masahiro Nishiyama, Aoi Kawamura, Shizuka Oikawa, Shoichi Tokumoto, Hiroshi Yamaguchi, Kazumi Tomioka, Kandai Nozu, Hiroki Mishina, Hiroaki Nagase
    Although the causes of neurodevelopmental disorders remain unknown, several environmental risk factors have attracted considerable attention. We conducted a retrospective, longitudinal, population-based cohort study using data from infant health examinations of children born to mothers with pregnancies between April 1, 2014 and March 31, 2016 in Kobe City to identify the perinatal factors associated with neurodevelopmental referrals in 3-year-old children. There were 15,223 and 1283 children in the normal and referral groups, respectively. Neurodevelopmental referrals at the health checkup for 3-year-old children were significantly associated with the lack of social support during pregnancy (adjusted odds ratio [aOR] 1.99, 99% CI 1.14-3.45, p = 0.001), history of psychiatric consultation (aOR 1.56, 99% CI 1.10-2.22, p = 0.001), no social assistance post-delivery (aOR 1.49, 99% CI 1.03-2.16, p = 0.006), Edinburgh Post-natal Depression Scale (EPDS) score ≥ 9 (aOR 1.36, 99% CI 1.01-1.84, p = 0.008), infant gender (male) (aOR 2.51, 99% CI 2.05-3.06, p < 0.001), and cesarean delivery (aOR 1.39, 99% CI 1.11-1.75, p < 0.001). In conclusion, this exploratory study in the general Japanese population identified six perinatal factors associated with neurodevelopmental referrals in 3-year-old children: infant gender (male), cesarean section, maternal history of psychiatric consultation, EPDS score ≥ 9, lack of social support during pregnancy, and no social assistance post-delivery.
    Feb. 2024, Scientific reports, 14(1) (1), 3492 - 3492, English, International magazine
    Scientific journal

  • 3歳児の睡眠習慣と小学1年生の学力および非認知能力との関連
    西山 将広, 野津 寛大, 永瀬 裕朗
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 188 - 188, Japanese

  • 検尿を契機とし持続する蛋白尿を指摘された症例における単一遺伝子異常同定に関する検討
    榊原 菜々, 猪野木 雄太, 市川 裕太, 田中 悠, 北角 英晶, 上田 知佳, 近藤 淳, 長野 智那, 堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 205 - 205, Japanese

  • 腎生検時における生理食塩水とリンゲル液の安全性の比較に関する検討
    田中 悠, 堀之内 智子, 猪野木 雄太, 市川 裕太, 北角 英晶, 上田 知佳, 近藤 淳, 榊原 菜々, 長野 智那, 野津 寛大
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 207 - 207, Japanese

  • Minigeneを用いたIn vitro splicing解析によるWT1遺伝子におけるIntron variantの病原性評価
    井上 誠也, 近藤 敦, 猪野木 雄太, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 榊原 菜々, 長野 智那, 堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 233 - 233, Japanese

  • 全エクソーム解析およびmRNA解析により診断に至ったAl-Raqad症候群の1例
    野崎 晴花, 榊原 菜々, 猪野木 雄太, 市川 裕太, 田中 悠, 北角 英晶, 上田 知佳, 近藤 淳, 長野 智那, 堀之内 智子, 森貞 直哉, 野津 寛大
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 234 - 234, Japanese

  • Alport症候群患者の診断における3歳児検尿の役割に関する検討
    北角 英晶, 猪野木 雄太, 市川 裕太, 田中 悠, 上田 知佳, 近藤 淳, 青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 236 - 236, Japanese

  • 当院における小児心停止症例に対する遺伝学的診断(Genetic autopsy)を含めた原因究明システムの構築
    松井 鋭, 黒澤 寛史, 花房 宏昭, 洪本 加奈, 坊 亮輔, 森貞 直哉, 吉田 牧子, 笠井 正志, 林 卓郎, 竹井 寛和, 谷澤 直子, 大西 康裕, 大西 理史, 宮脇 康輔, 松本 泰右, 長崎 靖, 田中 亮二郎, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 293 - 293, Japanese

  • Shohei Yoshimura, Yuichi Okata, Makoto Ooi, Tomoko Horinouchi, Serena Iwabuchi, Yasuyuki Kameoka, Aya Watanabe, Atsushi Kondo, Kotaro Uemura, Yuichiro Tomioka, Yoshitomo Samejima, Yumiko Nakai, Kandai Nozu, Yuzo Kodama, Yuko Bitoh
    Serum leucine-rich alpha-2 glycoprotein (LRG) has been utilized for adult inflammatory bowel disease (IBD); however, its efficacy in pediatric IBD remains unknown. The aim of this study was to compare the diagnostic accuracy of serum LRG for pediatric IBD with that of current inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This retrospective case-control study included pediatric patients, aged <16 years, who underwent colonoscopy and/or esophagogastroduodenoscopy between April 2017 and March 2022. All eligible patients were divided into two groups: patients with IBD, diagnosed with ulcerative colitis and Crohn's disease, and non-IBD controls. The optimal cut-off value of serum LRG for IBD diagnosis was determined from receiver operating characteristic analysis, and diagnostic accuracy of serum LRG was compared to serum ESR and CRP. A total of 53 patients (24 with IBD and 29 non-IBD controls) met the inclusion criteria. The cut-off value of serum LRG for IBD diagnosis was determined to be 19.5 μg/ml. At this cut-off value, serum LRG had a positive predictive value (PPV) of 0.80 and negative predictive value (NPV) of 0.88. In contrast, PPV and NPV were 0.78 and 0.70 for serum ESR and 0.82 and 0.72 for serum CRP, respectively. Serum LRG can be a potential diagnostic marker for pediatric IBD, with higher diagnostic accuracy than that of the conventional serum markers ESR and CRP.
    Jan. 2024, The Kobe journal of medical sciences, 69(4) (4), E122-E128, English, Domestic magazine
    Scientific journal

  • Tomohiro Sameshima, Mariko Ashina, Takuya Fukuda, Takumi Kido, Shinya Abe, Yuko Watanabe, Itsuko Sato, Yoshihiko Yano, Kenji Tanimura, Hiroaki Nagase, Kandai Nozu, Kazumichi Fujioka
    Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000-4999 mAU/mL), and 10.7% latent VK deficiency (200-999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p < 0.001). Gestational age correlated with PIVKA-II levels (r2 = 0.117, p < 0.0001). Median serum PIVKA-II levels and incidence of PIVKA-II-positive cases (≥ 50 mAU/mL, 16.4%) were lower at 5 days after birth than at birth, possibly reflecting the postnatal VK prophylaxis impact. Only one infant was diagnosed with VK deficiency bleeding (PIVKA-II levels, at birth: 10,567 mAU/mL; at day 5: 2418 mAU/mL). Thus, serum PIVKA-II levels after birth weakly correlated with gestational age. VK deficiency was more common in term infants than in preterm infants.
    Jan. 2024, Scientific reports, 14(1) (1), 921 - 921, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshinori Nambu, Taku Shirakawa, Kayo Osawa, Hisahide Nishio, Kandai Nozu, Masafumi Matsuo, Hiroyuki Awano
    Becker muscular dystrophy is caused by DMD mutations and is characterized by progressive muscle atrophy. The wide variations observed in muscle atrophy progression in Becker muscular dystrophy are considered multifactorial, including differences in mutations and environmental factors. In this case, two brothers, aged 2 and 3 years, had the identical DMD mutation, confirming their Becker muscular dystrophy diagnosis. They began using handrails when ascending and descending stairs at the age of 16 due to progressive muscular weakness. Over an 18-year follow-up, the older brother consistently had high serum creatine kinase levels, significantly over median levels. Muscle computed tomography finings revealed that the older brother’s gluteus maximus and vastus femoris cross-sectional areas were only half and one-third of the younger brother’s, respectively. The mean computed tomography values of gluteus maximus and vastus femoris were significantly lower in the older brother. Our report suggests that muscle atrophy in Becker muscular dystrophy cannot be solely explained by dystrophin mutation or environmental factors.
    SAGE Publications, Jan. 2024, SAGE Open Medical Case Reports, 12
    Scientific journal

  • 【腎臓学この1年の進歩】ネフリンとネフローゼ症候群
    飯島 一誠, 堀之内 智子, 長野 智那, 野津 寛大
    (一社)日本腎臓学会, Jan. 2024, 日本腎臓学会誌, 66(1) (1), 303 - 309, Japanese

  • 猪野木 雄太, 堀之内 智子, 田中 悠, 市川 裕太, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 長野 智那, 野津 寛大
    (一社)日本小児腎臓病学会, 2024, 日本小児腎臓病学会雑誌, 37, 92 - 93, Japanese

  • 向野 文貴, 松重 武志, 岡田 裕介, 橘高 節明, 星出 まどか, 森貞 直哉, 野津 寛大, 長谷川 俊史
    (一社)日本小児神経学会, Jan. 2024, 脳と発達, 56(1) (1), 70 - 70, Japanese

  • Yu Masuda, Takumi Kido, Mariko Ashina, Kandai Nozu, Kazumichi Fujioka
    2024, Pediatrics international : official journal of the Japan Pediatric Society, 66(1) (1), e15725, English, International magazine

  • Shoko Sonehara, Ryosuke Bo, Yoshinori Nambu, Kiiko Iketani, Tomoko Lee, Hideki Shimomura, Masaaki Ueda, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hisahide Nishio, Hiroyuki Awano
    Newborn screening (NBS) for spinal muscular atrophy (SMA) is necessary, as favorable outcomes can be achieved by treatment with disease-modifying drugs in early infancy. Although SMA-NBS has been initiated in Japan, its clinical results have not been fully reported. We report the findings of the initial 2.5 years of a pilot SMA-NBS of approximately 16,000 infants conducted from February 2021 in Hyogo Prefecture, Japan. Clinical data of 17 infants who tested positive were retrospectively obtained from the NBS follow-up centers participating in this multicenter cohort observational study. Genetic testing revealed 14 false positives, and three infants were diagnosed with SMA. Case 1 had two copies of survival motor neuron (SMN) 2 and showed SMA-related symptoms at diagnosis. Case 2 was asymptomatic, with two copies of SMN2. Asymptomatic case 3 had four copies of SMN2 exon 7, including the SMN1/2 hybrid gene. Cases 1 and 2 were treated within 1 month and case 3 at 8 months. All the patients showed improved motor function scores and did not require respiratory support. The identification of infants with SMA via NBS and early treatment improved their motor and respiratory outcomes. Thus, implementation of SMA-NBS at a nationwide scale should be considered.
    MDPI AG, Dec. 2023, Genes, 14(12) (12), 2211 - 2211
    Scientific journal

  • Masahiro Nishiyama, Yuki Kyono, Hiroshi Yamaguchi, Aoi Kawamura, Shizuka Oikawa, Shoichi Tokumoto, Kazumi Tomioka, Kandai Nozu, Hiroaki Nagase
    This study investigated the relationship between sleep habits in early childhood and academic performance and non-cognitive skills in the first grade. We retrospectively analyzed a longitudinal population-based cohort from birth through early childhood, up to elementary school, in Amagasaki City, Japan. The primary outcome was academic performance in the first grade. Other outcomes were self-reported non-cognitive skills. Overall, 4395 children were enrolled. Mean national language scores for children with bedtimes at 18:00-20:00, 21:00, 22:00, and ≥ 23:00 were 71.2 ± 19.7, 69.3 ± 19.4, 68.3 ± 20.1, and 62.5 ± 21.3, respectively. Multiple regression analysis identified bedtime at 3 years as a significant factor associated with academic performance. However, sleep duration was not significantly associated with academic performance. Bedtime at 3 years also affected non-cognitive skills in the first grade. Diligence decreased with a later bedtime (21:00 vs. 18:00-20:00; odds ratio [OR]: 1.98, 95% confidence interval [CI] 1.27-3.09; 22:00 vs. 18:00-20:00; OR: 2.15, 95% CI 1.37-3.38; ≥ 23:00 vs. 18:00-20:00; OR: 2.33, 95% CI 1.29-4.20). Thus, early bedtime at 3 years may be associated with a higher academic performance and better non-cognitive skills in the first grade. Optimum early-childhood sleep habits may positively impact academic future.
    Nov. 2023, Scientific reports, 13(1) (1), 20926 - 20926, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kandai Nozu, Mayumi Sako, Seiji Tanaka, Yuji Kano, Yoko Ohwada, Tamaki Morohashi, Riku Hamada, Yasufumi Ohtsuka, Masafumi Oka, Koichi Kamei, Aya Inaba, Shuichi Ito, Tomoyuki Sakai, Hiroshi Kaito, Yuko Shima, Kenji Ishikura, Hidefumi Nakamura, Koichi Nakanishi, Tomoko Horinouchi, Akihide Konishi, Takashi Omori, Kazumoto Iijima
    BACKGROUND: Only 80% of children with idiopathic nephrotic syndrome respond well to glucocorticoid therapy. Multidrug-resistant nephrotic syndrome (MRNS) is associated with a poor kidney prognosis. Several retrospective studies have identified rituximab as an effective treatment for MRNS; however, prospective studies are required to assess its efficacy and safety. METHODS: We conducted a multicenter, non-blinded, single-arm trial to investigate the efficacy and safety of rituximab in patients with childhood-onset MRNS who were resistant to cyclosporine and more than three courses of steroid pulse therapy. The enrolled patients received four 375 mg/m2 doses of rituximab in combination with baseline cyclosporine and steroid pulse therapy. The primary endpoint was a > 50% reduction in the urinary protein/creatinine ratio from baseline on day 169. Complete and partial remissions were also evaluated. RESULTS: Six patients with childhood-onset MRNS were enrolled. All patients were negative for pathogenic variants of podocyte-related genes. On day 169, five patients (83.3%) showed a > 50% reduction in the urinary protein/creatinine ratio, two patients showed partial remission, and two patients showed complete remission. No deaths occurred and severe adverse events occurred in two patients (infection in one patient and acute kidney injury in one patient). Three patients needed treatment for moderate-to-severe infection. CONCLUSIONS: The study treatment effectively reduced the urinary protein/creatinine ratio in patients with childhood-onset MRNS. The adverse events in this study were within the expected range; however, attention should be paid to the occurrence of infections.
    Nov. 2023, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 吉村 翔平, 大片 祐一, 堀之内 智子, 大井 充, 近藤 淳, 冨岡 雄一郎, 鮫島 由友, 中井 優美子, 渡邊 大輔, 児玉 裕三, 野津 寛大, 尾藤 祐子
    (一社)日本小児栄養消化器肝臓学会, Oct. 2023, 日本小児栄養消化器肝臓学会雑誌, 37(Suppl.) (Suppl.), 81 - 81, Japanese

  • Ryuichiro Hirayama, Kosuke Toyohara, Kei Watanabe, Takeya Otsuki, Toshikazu Araoka, Shin-Ichi Mae, Tomoko Horinouchi, Tomohiko Yamamura, Keisuke Okita, Akitsu Hotta, Kazumoto Iijima, Kandai Nozu, Kenji Osafune
    Abstract Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS.
    Springer Science and Business Media LLC, Sep. 2023, Communications Biology, 6(1) (1)
    Scientific journal

  • 意識障害を呈した小児に対する救急外来簡易脳波の原因疾患別特徴
    山口 宏, 上田 拓耶, 老川 静香, 徳元 翔一, 西山 将広, 丸山 あずさ, 野津 寛大, 永瀬 裕朗
    (一社)日本てんかん学会, Sep. 2023, てんかん研究, 41(2) (2), 326 - 326, Japanese

  • 長期緩下剤内服により偽性Gitelman症候群を発症し末期腎不全に至った1例
    近藤 淳, 吉矢 邦彦, 猪野木 雄太, 田中 悠, 北角 英晶, 上田 知佳, 榊原 菜々, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Sep. 2023, 日本腎臓学会誌, 65(6-W) (6-W), 783 - 783, Japanese

  • 洪本 加奈, 森貞 直哉, 野津 寛大, 大津 雅秀, 小林 大介
    (公社)日本整形外科学会, Sep. 2023, 日本整形外科学会雑誌, 97(9) (9), 613 - 613, Japanese

  • 免疫抑制剤治療を回避しえたLMX1Bのde novo変異によるネフローゼ症候群の一例
    三宅 崇文, 杉岡 清香, 松原 雄, 横井 秀基, 宮田 仁美, 野津 寛大, 柳田 素子
    (一社)日本腎臓学会, Sep. 2023, 日本腎臓学会誌, 65(6-W) (6-W), 770 - 770, Japanese

  • 詳細な遺伝子解析により診断に至った常染色体優性尿細管間質性腎疾患(ADTKD)の1例
    錦 惠那, 清水 真央, 渡邉 健太郎, 坂本 和雄, 河野 圭志, 後藤 俊介, 藤井 秀毅, 岡田 里枝子, 野津 寛大
    (一社)日本腎臓学会, Sep. 2023, 日本腎臓学会誌, 65(6-W) (6-W), 804 - 804, Japanese

  • Shotaro Inoue, Kaung Htet Nay Win, Cho Yee Mon, Tomoko Fujikawa, Sayaka Hyodo, Suguru Uemura, Toshiaki Ishida, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Akihiro Nishimura, Naoko Nakatani, Nanako Nino, Akihiro Tamura, Nobuyuki Yamamoto, Kandai Nozu, Noriyuki Nishimura
    More than half of patients with high-risk neuroblastoma (HR-NB) experience relapse/regrowth due to the activation of chemoresistant minimal residual disease (MRD). MRD in patients with HR-NB can be evaluated by quantitating neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow (BM) and peripheral blood (PB) samples. Although several sets of NB-mRNAs have been shown to possess a prognostic value for MRD in BM samples (BM-MRD), MRD in PB samples (PB-MRD) is considered to be low and difficult to evaluate. The present report describes an HR-NB case presenting higher PB-MRD than BM-MRD before 1st and 2nd relapse/regrowth. A 3-year-old female presented with an abdominal mass, was diagnosed with HR-NB, and treated according to the nationwide standard protocol for HR-NB. Following systemic induction and consolidation therapy with local therapy, the patient achieved complete remission but experienced a 1st relapse/regrowth 6 months after maintenance therapy. The patient partially responded to salvage chemotherapy and anti-GD2 immunotherapy but had a 2nd relapse/regrowth 14 months after the 1st relapse/regrowth. Consecutive PB-MRD and BM-MRD monitoring revealed that PB-MRD was lower than BM-MRD at diagnosis (100 times) and 1st and 2nd relapse/regrowth (1,000 and 3 times) but became higher than BM-MRD before 1st and 2nd relapse/regrowth. The present case highlights that PB-MRD can become higher than BM-MRD before relapse/regrowth of patients with HR-NB.
    Sep. 2023, Oncology letters, 26(3) (3), 369 - 369, English, International magazine

  • Frontometaphyseal dysplasia type 1の遺伝学的診断と遺伝カウンセリング
    洪本 加奈, 森貞 直哉, 野津 寛大, 大津 雅秀, 小林 大介
    (公社)日本整形外科学会, Sep. 2023, 日本整形外科学会雑誌, 97(9) (9), 613 - 613, Japanese

  • Yuko Shima, Hironobu Mukaiyama, Yu Tanaka, Wataru Shimabukuro, Kandai Nozu, Hiroshi Kaito, Ryojiro Tanaka, Mayumi Sako, Kazumoto Iijima, Daisuke Tokuhara, Norishige Yoshikawa, Koichi Nakanishi
    BACKGROUND: Proteinuria remission is the most significant predictive factor for kidney outcome in childhood IgA nephropathy (c-IgAN). Even if proteinuria remission can be obtained, some patients have recurrence of proteinuria in the long-term. METHODS: This is a retrospective analysis of 312 cases of proteinuria remission among 538 consecutive children with biopsy-proven IgAN from 1976 to 2013. To elucidate the incidence and factors related to recurrence of proteinuria in c-IgAN, we compare clinical and pathological findings between patients with and without recurrence of proteinuria. RESULTS: Among 312 patients with remission of proteinuria, 91 (29.2%) had recurrence of proteinuria within the observation period (median 8 years). Using a multivariate Cox regression analysis, significant factors associated with recurrence of proteinuria were onset age (HR 1.13 [95%CI: 1.05-1.22], P = 0.002) and presence of hematuria after proteinuria remission (HR 2.11 [95%CI: 1.30-3.45], P = 0.003). The Kaplan-Meier analysis showed significant differences in CKD G3a-G5-free survival between the patients with no-recurrence of proteinuria, recurrence of proteinuria and non-proteinuria remission (P < 0.0001, log-rank test). Kidney survival was 100% in no-recurrence of proteinuria, 92.2% in recurrence of proteinuria, and 65.6% in non-proteinuria remission at 15 years. Cox analyses adjusted by proteinuria remission showed that recurrence of proteinuria (HR 03.10e9 [95%CI: NA], P = 0.003) was a significant factor associated with progression to CKD G3a-G5 in all patients with c-IgAN. CONCLUSIONS: Approximately 30% of patients with proteinuria remission had recurrence of proteinuria regardless of treatment. Both remission and recurrence of proteinuria are significant prognostic factors for kidney outcome. A higher resolution version of the Graphical abstract is available as Supplementary information.
    Aug. 2023, Pediatric nephrology (Berlin, Germany), English, International magazine
    Scientific journal

  • Hiroko Ueda, Quynh Thuy Huong Tran, Linh Nguyen Truc Tran, Koichiro Higasa, Yoshiki Ikeda, Naoyuki Kondo, Masaki Hashiyada, Chika Sato, Yoshinori Sato, Akira Ashida, Saori Nishio, Yasunori Iwata, Hiroyuki Iida, Daisuke Matsuoka, Yoshihiko Hidaka, Kenji Fukui, Suzu Itami, Norihito Kawashita, Keisuke Sugimoto, Kandai Nozu, Motoshi Hattori, Hiroyasu Tsukaguchi
    Abstract Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot–Marie–Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotypes
    Springer Science and Business Media LLC, Jul. 2023, Scientific Reports, 13(1) (1)
    [Refereed]
    Scientific journal

  • 花房 宏昭, 森貞 直哉, 長坂 美和子, 叶 明娟, 野口 裕子, 長野 智那, 野津 寛大, 粟野 宏之
    Basilicata-Akhtar症候群はMSL3のヘテロ接合性もしくはヘミ接合性変異によるまれなX連鎖性疾患で乳児期からの全般性発達遅滞,経口摂取障害,筋緊張低下などを特徴とする.これまでに約40例が報告されているが,本邦では報告されていない.今回,本邦初のBasilicata-Akhtar症候群の例を報告する.症例は日本人の7歳男児で全般性発達遅滞,筋緊張の低下,経口摂取障害を呈した.身体所見として内眼角贅皮,眼角解離,眼瞼裂斜下,広い鼻梁,上向きの鼻孔,テント状の上口唇,垂れた耳,短い手足,先細りの指,外反膝,扁平足,胸郭変形,側彎を認めた.アレイCGH解析で,MSL3の全コード領域と,ARHGAP6の5'側のみを含んだXp22.2のヘミ接合性欠失を認めた.本症例の表現型はこれまでに報告されているBasilicata-Akhtar症候群に一致するものであった.本症例の病態は機能喪失を引き起こすMSL3の全コード領域の欠失であった.本症例と同様にMSL3の全コード領域とARHGAP6の5'領域のみを欠失するBasilicata-Akhtar症候群の女児2例の報告があるが,ヌリソミー男児例は過去に報告がない.この欠失を有する3例とMSL3の一塩基バリアントを有する既報告例との間に,臨床症状の違いは認められなかった.本症候群の機能的特徴を明らかにするためには,多様な民族から様々なバリアントを持つ症例をさらに集積することが重要である.(著者抄録)
    (一社)日本小児神経学会, Jul. 2023, 脳と発達, 55(4) (4), 279 - 282, English

  • 花房 宏昭, 森貞 直哉, 長坂 美和子, 叶 明娟, 野口 裕子, 長野 智那, 野津 寛大, 粟野 宏之
    Basilicata-Akhtar症候群はMSL3のヘテロ接合性もしくはヘミ接合性変異によるまれなX連鎖性疾患で乳児期からの全般性発達遅滞,経口摂取障害,筋緊張低下などを特徴とする.これまでに約40例が報告されているが,本邦では報告されていない.今回,本邦初のBasilicata-Akhtar症候群の例を報告する.症例は日本人の7歳男児で全般性発達遅滞,筋緊張の低下,経口摂取障害を呈した.身体所見として内眼角贅皮,眼角解離,眼瞼裂斜下,広い鼻梁,上向きの鼻孔,テント状の上口唇,垂れた耳,短い手足,先細りの指,外反膝,扁平足,胸郭変形,側彎を認めた.アレイCGH解析で,MSL3の全コード領域と,ARHGAP6の5'側のみを含んだXp22.2のヘミ接合性欠失を認めた.本症例の表現型はこれまでに報告されているBasilicata-Akhtar症候群に一致するものであった.本症例の病態は機能喪失を引き起こすMSL3の全コード領域の欠失であった.本症例と同様にMSL3の全コード領域とARHGAP6の5'領域のみを欠失するBasilicata-Akhtar症候群の女児2例の報告があるが,ヌリソミー男児例は過去に報告がない.この欠失を有する3例とMSL3の一塩基バリアントを有する既報告例との間に,臨床症状の違いは認められなかった.本症候群の機能的特徴を明らかにするためには,多様な民族から様々なバリアントを持つ症例をさらに集積することが重要である.(著者抄録)
    (一社)日本小児神経学会, Jul. 2023, 脳と発達, 55(4) (4), 279 - 282, English

  • Ryota Suzuki, Nana Sakakibara, Yuta Ichikawa, Hideaki Kitakado, Chika Ueda, Yu Tanaka, Eri Okada, Atsushi Kondo, Shinya Ishiko, Shingo Ishimori, China Nagano, Tomohiko Yamamura, Tomoko Horinouchi, Takayuki Okamoto, Kandai Nozu
    Elsevier {BV}, Jul. 2023, Kidney International Reports, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Sadayuki Nagai, Tomoko Horinouchi, Takeshi Ninchoji, Yuta Ichikawa, Yu Tanaka, Hideaki Kitakado, Chika Ueda, Atsushi Kondo, Yuya Aoto, Nana Sakakibara, Hiroshi Kaito, Ryojiro Tanaka, Yuko Shima, Junya Fujimura, Naohiro Kamiyoshi, Shingo Ishimori, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Patients with severe IgA vasculitis with nephritis (IgAVN) typically receive aggressive therapy as an initial approach. We have consistently performed combination therapy including corticosteroids and immunosuppressants as initial therapy for severe IgAVN over a 20-year-plus period, with only minor changes to the treatment protocol. This study seeks to reveal the efficacy of combination therapy for severe IgAVN. METHODS: We retrospectively studied 50 Japanese children diagnosed between 1996 and 2019 with clinicopathologically severe IgAVN who were defined as ISKDC classification grade IIIb-V and/or serum albumin < 2.5 g/dL. RESULTS: The median age at the onset of IgAVN was 8.0 years (IQR: 6.0-10.0). At biopsy, 44% of patients had nephrotic syndrome and 14% had kidney dysfunction. All patients were treated with combination therapy after biopsy. Abnormal proteinuria resolved after initial therapy in all 50 patients. However, eight patients (16%) had recurrence of proteinuria. Abnormal proteinuria was again resolved in three of these patients with additional treatment. At the last follow-up (median 59.5 months; IQR, 26.2-84.2), the median urine protein-to-creatine ratio was 0.08 g/gCr (IQR, 0.05-0.15), and only one patient had kidney dysfunction. CONCLUSIONS: Combination therapy provided good kidney outcomes for Japanese children with severe IgAVN. Even including recurrent cases, the degree of proteinuria was slight, and kidney function was good at the last follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
    Jun. 2023, Pediatric nephrology (Berlin, Germany), English, International magazine
    Scientific journal

  • 【遺伝を考える】(II章)遺伝学的診断 個別診療分野における遺伝学的診断の進歩 腎・泌尿器領域
    飯島 一誠, 堀之内 智子, 野津 寛大
    (公社)日本医師会, Jun. 2023, 日本医師会雑誌, 152(特別1) (特別1), S146 - S150, Japanese

  • 花房 宏昭, 田中 敬子, 濱 真奈美, 金原 史朗, 益子 尚久, 坊 亮輔, 國久 智成, 粟野 宏之, 清田 尚臣, 久保 亮治, 南 博信, 野津 寛大
    (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 139 - 139, Japanese

  • 濱 真奈美, 花房 宏昭, 田中 敬子, 冨本 雅子, 尾崎 可奈, 今福 仁美, 坊 亮輔, 國久 智成, 久保 亮治, 粟野 宏之, 野津 寛大
    (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 149 - 149, Japanese

  • 益子 尚久, 花房 宏昭, 濱 真奈美, 田中 敬子, 前田 美亜, 冨本 雅子, 今福 仁美, 粟野 宏之, 出口 雅士, 寺井 義人, 野津 寛大
    (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 156 - 156, Japanese

  • 田中 敬子, 花房 宏昭, 濱 真奈美, 千葉 公嗣, 坊 亮輔, 國久 智成, 久保 亮治, 粟野 宏之, 野津 寛大
    (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 163 - 163, Japanese

  • 朝貝 芳貴, 洪本 加奈, 森貞 直哉, 野津 寛大
    (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 117 - 117, Japanese

  • 新生児期に低ナトリウム血症を来した常染色体潜性多発性嚢胞腎の症例
    石見 壮史, 熊野 晶理, 武鑓 真司, 中山 尋文, 藤原 誠, 大幡 泰久, 北岡 太一, 隅 清彰, 森貞 直哉, 野津 寛大, 大薗 恵一, 窪田 拓生
    大阪小児科学会, Jun. 2023, 大阪小児科学会誌, 40(2) (2), 9 - 9, Japanese

  • Hiroaki Hanafusa, Hiroshi Yamaguchi, Hidehito Kondo, Miwako Nagasaka, Ming Juan Ye, Shizuka Oikawa, Shoichi Tokumoto, Kazumi Tomioka, Masahiro Nishiyama, Naoya Morisada, Masafumi Matsuo, Kandai Nozu, Hiroaki Nagase
    OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a serious condition that requires intensive care and is associated with a high mortality rate. However, its pathogenesis remains unclear. In the present study, a genetic analysis was performed to determine the genetic background of patients with clinically suspected Dravet syndrome (DS) who developed HSES. METHODS: Whole exome sequencing was performed, followed by minigene analysis of the intron variant detected by whole exome sequencing to confirm its effect on splicing. RESULTS: Whole exome sequencing revealed a novel 21-bp deletion in intron 3 of SCN1A NM_001165963.4 (NC_000002.11:g.166073675_166073695del). This deletion was not found in the patient's parents and was proven to be de novo. Minigene analysis revealed an aberrant mRNA lacking 40 and 106 bp from the 5' end of exon 4 of SCN1A. Therefore, we diagnosed this case as DS due to the deletion in intron 3 of SCN1A. CONCLUSIONS: We report a case of DS with HSES caused by a 21-bp deletion in the intron of SCN1A that was confirmed by minigene analysis. The present case met Levin's criteria for HSES and the splicing analysis of SCN1A is an important finding. This study has important implications for understanding HSES pathogenesis.
    Jun. 2023, Brain & development, 45(6) (6), 317 - 323, English, International magazine
    Scientific journal

  • Eri Okada, Tomoko Horinouchi, Tomohiko Yamamura, Yuya Aoto, Ryota Suzuki, Yuta Ichikawa, Yu Tanaka, Chika Masuda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, Shinya Ishiko, China Nagano, Shingo Ishimori, Joichi Usui, Kunihiro Yamagata, Masafumi Matsuo, Kandai Nozu
    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by insufficient α-galactosidase A (GLA) activity resulting from variants in the GLA gene, which leads to glycosphingolipid accumulation and life-threatening, multi-organ complications. Approximately 50 variants have been reported that cause splicing abnormalities in GLA. Most were found within canonical splice sites, which are highly conserved GT and AG splice acceptor and donor dinucleotides, whereas one-third were located outside canonical splice sites, making it difficult to interpret their pathogenicity. In this study, we aimed to investigate the genetic pathogenicity of variants located in non-canonical splice sites within the GLA gene. METHODS: 13 variants, including four deep intronic variants, were selected from the Human Gene Variant Database Professional. We performed an in vitro splicing assay to identify splicing abnormalities in the variants. RESULTS: All candidate non-canonical splice site variants in GLA caused aberrant splicing. Additionally, all but one variant was protein-truncating. The four deep intronic variants generated abnormal transcripts, including a cryptic exon, as well as normal transcripts, with the proportion of each differing in a cell-specific manner. CONCLUSIONS: Validation of splicing effects using an in vitro splicing assay is useful for confirming pathogenicity and determining associations with clinical phenotypes.
    May 2023, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 京野 由紀, 西山 将広, 老川 静香, 徳元 翔一, 山口 宏, 冨岡 和美, 三品 浩基, 野津 寛大, 永瀬 裕朗
    (公社)日本小児保健協会, May 2023, 小児保健研究, 82(講演集) (講演集), 138 - 138, Japanese

  • 3歳時の就寝時刻または睡眠時間と小学1年生の学力との関連 尼崎市の人口ベースの研究
    西山 将広, 京野 由紀, 川村 葵, 老川 静香, 徳元 翔一, 山口 宏, 冨岡 和美, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S284 - S284, Japanese

  • 山口 宏, 花房 宏昭, 老川 静香, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S318 - S318, Japanese

  • 母乳中に自己抗原反応性IgAが認められたNeonatal linear IgA bullous dermatosisの1例
    橋本 真哉, 福本 毅, 吉田 憲司, 堀之内 智子, 市川 裕太, 田中 悠, 藤村 順也, 野津 寛大, 石河 晃, 久保 亮治
    (公社)日本皮膚科学会, May 2023, 日本皮膚科学会雑誌, 133(5) (5), 1355 - 1355, Japanese

  • 市川 裕太, 榊原 菜々, 田中 悠, 上田 知佳, 北角 英晶, 近藤 淳, 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 95 - 95, Japanese

  • X染色体連鎖型Alport症候群女性における、X染色体不活化パターン・表現型相関
    鈴木 諒太, 榊原 菜々, 市川 裕太, 北角 英晶, 上田 知佳, 田中 悠, 岡田 絵里, 近藤 淳, 石森 真吾, 堀之内 智子, 岡本 孝之, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 96 - 96, Japanese

  • LAMB2関連疾患における臨床的特徴と遺伝型・表現型相関
    鈴木 諒太, 榊原 菜々, 市川 裕太, 北角 英晶, 上田 知佳, 田中 悠, 岡田 絵里, 近藤 淳, 石森 真吾, 堀之内 智子, 岡本 孝之, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 96 - 96, Japanese

  • 近藤 淳, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 鈴木 諒太, 岡田 絵里, 青砥 悠哉, 榊原 菜々, 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 115 - 115, Japanese

  • 加古 優香, 堀之内 智子, 田中 悠, 市川 裕太, 上田 知佳, 近藤 淳, 榊原 菜々, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 121 - 121, Japanese

  • 石森 真吾, 堀之内 智子, 山村 智彦, 藤村 順也, 神吉 直宙, 貝藤 裕史, 田中 百合子, 松倉 裕喜, 島袋 渡, 島 友子, 河口 亜津彩, 荒木 義則, 中西 浩一, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 124 - 124, Japanese

  • 上田 知佳, 堀之内 智子, 市川 裕太, 田中 悠, 北角 英晶, 近藤 淳, 榊原 菜々, 藤村 順也, 神吉 直宙, 石森 真吾, 貝藤 裕史, 島 友子, 吉川 徳茂, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 126 - 126, Japanese

  • 青砥 悠哉, 岡田 絵里, 市川 裕太, 田中 悠, 北角 英晶, 上田 知佳, 近藤 淳, 榊原 菜々, 堀之内 智子, 忍頂寺 毅史, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 131 - 131, Japanese

  • 井上 誠也, 近藤 淳, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 鈴木 諒太, 岡田 絵里, 榊原 菜々, 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 134 - 134, Japanese

  • 堀之内 智子, 上田 知佳, 北角 英晶, 市川 裕太, 田中 悠, 近藤 淳, 榊原 菜々, 吉川 徳茂, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 142 - 142, Japanese

  • 野崎 晴花, 榊原 菜々, 田中 悠, 市川 裕太, 北角 英昌, 上田 知佳, 近藤 淳, 堀之内 智子, 猪野木 雄太, 亀井 宏一, 森貞 直哉, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 166 - 166, Japanese

  • 田中 悠, 平田 優, 木越 隆晶, 池田 洋一郎, 榊原 菜々, 市川 裕太, 上田 知佳, 北角 英晶, 近藤 淳, 堀之内 智子, 南 裕佳, 平本 龍吾, 稲垣 徹史, 森貞 直哉, 野津 寛大
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 187 - 187, Japanese

  • 亀井 宏一, 野津 寛大, 堀之内 智子, 西 健太朗, 藤田 直也, 櫻谷 浩志, 貝塚 裕史, 冨樫 勇人, 濱田 陸, 島 友子, 吉川 徳茂
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 198 - 198, Japanese

  • COL4A5遺伝子におけるsplicing異常をきたすvariantsの特徴と臨床型との相関に関する研究
    青砥 悠哉, 岡田 絵里, 堀之内 智子, 忍頂寺 毅史, 飯島 一誠, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 238 - 238, Japanese

  • 本邦における2型Bartter症候群の臨床的特徴とGenotype/Phenotype Correlation
    近藤 淳, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 青砥 悠哉, 榊原 菜々, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 239 - 239, Japanese

  • CUBN異常症の遺伝学的特徴と臨床像
    榊原 菜々, 市川 裕太, 田中 悠, 鈴木 諒太, 北角 英晶, 上田 知佳, 近藤 淳, 岡田 絵里, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 260 - 260, Japanese

  • Podocalyxin異常に伴う腎炎発症機序の検討
    北角 英晶, 榊原 菜々, 市川 裕太, 田中 悠, 上田 知佳, 近藤 淳, 鈴木 諒太, 岡田 絵里, 堀之内 智子, 藤丸 季可, 前田 亮, 稲熊 大城, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 261 - 261, Japanese

  • 当院で診断したMAFB異常4例と腎症に関する考察
    田中 悠, 平田 優, 木越 隆晶, 榊原 菜々, 市川 裕太, 北角 英晶, 近藤 淳, 堀之内 智子, 南 裕佳, 平本 龍吾, 稲垣 徹史, 森貞 直哉, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 261 - 261, Japanese

  • X染色体連鎖型Alport症候群女性における,X染色体不活化・表現型相関
    鈴木 諒太, 榊原 菜々, 市川 裕太, 北角 英晶, 上田 知佳, 田中 悠, 岡田 絵里, 近藤 淳, 石森 真吾, 堀之内 智子, 岡本 孝之, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 262 - 262, Japanese

  • 小児C3腎炎の後方視的検討
    上田 知佳, 堀之内 智子, 市川 裕太, 田中 悠, 北角 英晶, 近藤 淳, 榊原 菜々, 藤村 順也, 神吉 直宙, 石森 真吾, 貝藤 裕史, 島 友子, 吉川 徳茂, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 323 - 323, Japanese

  • 小児IgA腎症の肉眼的血尿発作に伴う急性腎障害発症に鉄とマクロファージが関与する 多機関共同研究
    石森 真吾, 堀之内 智子, 藤村 順也, 神吉 直宙, 貝藤 裕史, 田中 百合子, 松倉 裕喜, 島袋 渡, 島 友子, 河口 亜津彩, 荒木 義則, 中西 浩一, 野津 寛大
    (一社)日本腎臓学会, May 2023, 日本腎臓学会誌, 65(3) (3), 335 - 335, Japanese

  • 花房 宏昭, 山口 宏, 老川 静香, 徳元 翔一, 冨岡 和美, 西山 将広, 長坂 美和子, 近藤 秀仁, 森貞 直哉, 松尾 雅文, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S302 - S302, Japanese

  • 曽根原 晶子, 坊 亮輔, 池谷 紀衣子, 南部 静紀, 老川 静香, 徳元 翔一, 山口 宏, 冨岡 和美, 永瀬 裕朗, 竹島 泰弘, 飯島 一誠, 野津 寛大, 西尾 久英, 粟野 宏之
    (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S319 - S319, Japanese

  • 小山 結実, Suico Mary Ann, 加世田 将大, 桑水流 淳, 三宮 裕也, 堀園 潤, 津波古 遥希, 尾脇 あいみ, 佐藤 諒一, 白神 正博, 首藤 剛, 山村 智彦, 野津 寛大, 甲斐 広文
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 94 - 94, Japanese

  • 小山 結実, Suico Mary Ann, 加世田 将大, 桑水流 淳, 三宮 裕也, 堀園 潤, 津波古 遥希, 尾脇 あいみ, 佐藤 諒一, 白神 正博, 首藤 剛, 山村 智彦, 野津 寛大, 甲斐 広文
    (一社)日本小児腎臓病学会, May 2023, 日本小児腎臓病学会雑誌, 36(Suppl.) (Suppl.), 94 - 94, Japanese

  • Georgia Malakasioti, Daniela Iancu, Anastasiia Milovanova, Alexey Tsygin, Tomoko Horinouchi, China Nagano, Kandai Nozu, Koichi Kamei, Shuichiro Fujinaga, Kazumoto Iijima, Rajiv Sinha, Biswanath Basu, William Morello, Giovanni Montini, Aoife Waters, Olivia Boyer, Zeynep Yürük Yıldırım, Sibel Yel, İsmail Dursun, Hugh J McCarthy, Marina Vivarelli, Larisa Prikhodina, Martine T P Besouw, Eugene Yu-Hin Chan, Wenyan Huang, Markus J Kemper, Sebastian Loos, Chanel Prestidge, William Wong, Galia Zlatanova, Rasmus Ehren, Lutz T Weber, Hassib Chehade, Nakysa Hooman, Marcin Tkaczyk, Małgorzata Stańczyk, Michael Miligkos, Kjell Tullus
    While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.
    May 2023, Kidney international, 103(5) (5), 962 - 972, English, International magazine
    Scientific journal

  • Eri Okada, Naoya Morisada, Tomoko Horinouchi, Hideki Fujii, Takayuki Tsuji, Masayoshi Miura, Hideyuki Katori, Masashi Kitagawa, Kunio Morozumi, Takanobu Toriyama, Yuki Nakamura, Ryuta Nishikomori, Sadayuki Nagai, Atsushi Kondo, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Shingo Ishimori, Joichi Usui, Kunihiro Yamagata, Kazumoto Iijima, Toshiyuki Imasawa, Kandai Nozu
    [This corrects the article DOI: 10.1016/j.ekir.2021.12.037.].
    May 2023, Kidney international reports, 8(5) (5), 1127 - 1129, English, International magazine

  • Alexandra Barry, Michelle T McNulty, Xiaoyuan Jia, Yask Gupta, Hanna Debiec, Yang Luo, China Nagano, Tomoko Horinouchi, Seulgi Jung, Manuela Colucci, Dina F Ahram, Adele Mitrotti, Aditi Sinha, Nynke Teeninga, Gina Jin, Shirlee Shril, Gianluca Caridi, Monica Bodria, Tze Y Lim, Rik Westland, Francesca Zanoni, Maddalena Marasa, Daniel Turudic, Mario Giordano, Loreto Gesualdo, Riccardo Magistroni, Isabella Pisani, Enrico Fiaccadori, Jana Reiterova, Silvio Maringhini, William Morello, Giovanni Montini, Patricia L Weng, Francesco Scolari, Marijan Saraga, Velibor Tasic, Domenica Santoro, Joanna A E van Wijk, Danko Milošević, Yosuke Kawai, Krzysztof Kiryluk, Martin R Pollak, Ali Gharavi, Fangmin Lin, Ana Cristina Simœs E Silva, Ruth J F Loos, Eimear E Kenny, Michiel F Schreuder, Aleksandra Zurowska, Claire Dossier, Gema Ariceta, Magdalena Drozynska-Duklas, Julien Hogan, Augustina Jankauskiene, Friedhelm Hildebrandt, Larisa Prikhodina, Kyuyoung Song, Arvind Bagga, Hae Cheong 2nd, Gian Marco Ghiggeri, Prayong Vachvanichsanong, Kandai Nozu, Dongwon Lee, Marina Vivarelli, Soumya Raychaudhuri, Katsushi Tokunaga, Simone Sanna-Cherchi, Pierre Ronco, Kazumoto Iijima, Matthew G Sampson
    Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
    Apr. 2023, Nature communications, 14(1) (1), 2481 - 2481, English, International magazine
    Scientific journal

  • Yuta Ichikawa, Tomoko Horinouchi, Yu Tanaka, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, Norishige Yoshikawa, Kandai Nozu
    A Japanese boy developed nephrotic syndrome (NS) and had microscopic hematuria at 8 years old. Renal biopsy was performed. Light microscopy study revealed mesangial proliferation and all immunofluorescent stains (including IgA) were negative, so he was diagnosed with non-IgA diffuse mesangial proliferation (DMP). Complete remission was achieved at 13 days after the initiation of oral prednisolone, and hematuria also disappeared 3 days later, but the patient developed frequently relapsing nephrotic syndrome. Cyclosporine A (CyA) was introduced at 10 years old, and there were no relapses between then and when it was discontinued at 12 years old. A second renal biopsy revealed minimal change without CyA nephrotoxicity. However, there was repeated relapse of NS after discontinuation, so CyA was reintroduced 8 months later, and NS remained in remission thereafter. Microscopic hematuria appeared at 13 years old, however, with gross hematuria appearing at the time of infection. A third renal biopsy revealed mesangial proliferation with IgA-dominant deposition, so the patient was diagnosed with IgA nephropathy. Currently (14 years old), CyA treatment has been discontinued and the patient is undergoing lisinopril therapy for IgA nephropathy, but there are still relapses of NS. To the best of our knowledge, there have been no previous reports of a patient with non-IgA DMP at the onset of NS who had later development of IgA nephropathy. The patient showed non-IgA DMP at the onset, suggesting that NS with non-IgA DMP and IgA nephropathy has some common pathophysiology. Treatment for NS, such as PSL and/or CyA treatment, may suppress the clinical manifestation of late IgA nephropathy.
    Apr. 2023, CEN case reports, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • サイトメガロウイルス既感染母体から出生し,尿濾紙スクリーニング検査を契機に診断に至った症候性サイトメガロウイルス感染症の1新生児例
    金 潔駿, 阿部 真也, 川村 葵, 垂井 智前, 城戸 拓海, 京野 由紀, 菅 秀太郎, 仲宗根 瑠花, 芦名 満理子, 藤岡 一路, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 618 - 618, Japanese

  • 当院での脳症関連遺伝子パネルを用いた疾患関連遺伝子の同定の試み
    山口 宏, 花房 宏昭, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 628 - 628, Japanese

  • 新型コロナワクチン接種後に血尿を伴うネフローゼ症候群を発症した1例
    北角 英晶, 堀之内 智子, 増田 知佳, 近藤 淳, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 626 - 627, Japanese

  • Acetazolamide内服と生活指導で発作予防可能であった低カリウム性周期性四肢麻痺の1例
    増田 祐, 堀之内 智子, 近藤 淳, 市川 裕太, 田中 悠, 北角 英晶, 増田 知佳, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 633 - 633, Japanese

  • 堀之内 智子, 野津 寛大
    ＜文献概要＞Alport症候群はCOL4A3/4/5遺伝子の異常により発症する進行性遺伝性腎症である.持続的血尿に加え,遺伝子変異や病理組織学的所見,家族歴や眼病変・難聴等に基づいて診断される.治療薬としてはRAS阻害薬が一般的だが,SGLT2阻害薬の効果も今後期待される.
    (株)診断と治療社, Apr. 2023, 小児科診療, 86(春増刊) (春増刊), 737 - 738, Japanese

  • 当院で診断したMAFB異常4例のまとめと腎症に関する考察
    田中 悠, 平田 優, 木越 隆晶, 榊原 菜々, 市川 裕太, 北角 英晶, 近藤 淳, 堀之内 智子, 南 裕佳, 平本 龍吾, 稲垣 徹史, 森貞 直哉, 野津 寛大
    発達腎研究会, Apr. 2023, 発達腎研究会誌, 30(1) (1), 15 - 16, Japanese

  • 汎血球減少と斜指を契機に診断したMECOM関連症候群の女児
    平場 裕美, 二野 菜々子, 相馬 健人, 増田 知佳, 北角 英晶, 中谷 尚子, 呉 東祐, 高寺 明弘, 田村 彰広, 山本 暢之, 森沢 猛, 西村 範行, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 625, Japanese

  • 血性鼻汁をきっかけに診断したLCHの男児
    石川 達大, 井上 翔太郎, 西村 明紘, 中谷 尚子, 二野 菜々子, 田村 彰広, 山本 暢之, 西村 範行, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 632 - 632, Japanese

  • 近藤 淳, 堀之内 智子, 岡本 典大, 吉村 翔平, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 榊原 菜々, 渡邊 大輔, 星 奈美子, 大片 祐一, 大井 充, 尾藤 祐子, 児玉 裕三, 野津 寛大
    (一社)日本小児栄養消化器肝臓学会, Apr. 2023, 日本小児栄養消化器肝臓学会雑誌, 37(1) (1), 35 - 35, Japanese

  • COVID-19感染症を契機に急性増悪した全身型重症筋無力症の女児例
    金谷 真吾, 岩本 宗矩, 山口 宏, 南部 静紀, 徳元 翔一, 坊 亮輔, 冨岡 和美, 西山 将広, 粟野 宏之, 野津 寛大, 永瀬 裕朗
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 627 - 627, Japanese

  • アダリムマブを導入した潰瘍性大腸炎の12歳男児例
    久野 春香, 堀之内 智子, 近藤 淳, 宮崎 はる香, 北角 英晶, 増田 知佳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 具 潤亜, 大片 祐一, 大井 充, 尾藤 祐子, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 621 - 621, Japanese

  • 一過性の細胞免疫不全所見を認めた超早期発症型炎症性腸疾患の1例
    福田 拓弥, 堀之内 智子, 近藤 淳, 宮崎 はる香, 田村 彰広, 大片 祐一, 増田 知佳, 北角 英晶, 具 潤亜, 渡邉 大輔, 星 奈美子, 榊原 菜々, 山本 暢之, 大井 充, 尾藤 祐子, 森 一越, 野津 寛大
    (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 626, Japanese

  • 近藤 淳, 堀之内 智子, 岡本 典大, 吉村 翔平, 市川 裕太, 田中 悠, 上田 知佳, 北角 英晶, 榊原 菜々, 渡邊 大輔, 星 奈美子, 大片 祐一, 大井 充, 尾藤 祐子, 児玉 裕三, 野津 寛大
    (一社)日本小児栄養消化器肝臓学会, Apr. 2023, 日本小児栄養消化器肝臓学会雑誌, 37(1) (1), 35 - 35, Japanese

  • Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hiroyuki Awano
    The authors wish to make the following correction to this paper [...].
    Mar. 2023, Genes, 14(3) (3), English, International magazine

  • Kana Hiromoto, Naoya Morisada, Shinya Tairaku, Kandai Nozu, Kazumoto Iijima, Toru Funakoshi
    We report here a fatal oligohydramnios case, which was suspected due to autosomal recessive polycystic kidney disease at first, but genetic analysis using chorionic tissue and umbilical cord after stillbirth led to the diagnosis of 17q12 deletion syndrome. Subsequent genetic analysis of the parents showed no 17q12 deletion. In this case, if the fetus had autosomal recessive polycystic kidney disease, the recurrence rate in the next pregnancy was suspected to be 25%, but since it was a de novo autosomal dominant disorder, the recurrence rate is extremely low. When a fetal dysmorphic abnormality is detected, a genetic autopsy not only helps to understand the cause but also provides information about the recurrence rate. This information is important for the next pregnancy. A genetic autopsy is useful in cases of fetal deaths or abortions resulting from fetal dysmorphic abnormalities.
    Mar. 2023, The journal of obstetrics and gynaecology research, English, International magazine

  • Yuko Fujii, Hideki Matsumura, Akihiko Shirasu, Hyogo Nakakura, Satoshi Yamazaki, Tetsufumi Kanazawa, Nanako Saito, Hajime Hirano, Haruhito Azuma, Kandai Nozu, Akira Ashida
    BackgroundAutism spectrum disorder (ASD) is a common communication disorder, with an incidence rate of 3%. In most cases, clinicians can diagnose ASD in a single outpatient visit. However, in the case of ASD patients without intellectual disability, clinicians are sometimes unaware for a prolonged period that a patient has ASD. In such cases, delayed diagnosis can lead to serious complications.Case presentationAn 18-year-old boy had repeated severe complications of peritoneal dialysis. At the age of 9, the patient presented with proteinuria, and 5 years later, he developed end-stage kidney disease. Percutaneous renal biopsy and the clinical symptoms revealed focal segmental glomerulosclerosis with Charcot-Marie-Tooth disease due to a gene mutation in INF2. Peritoneal dialysis was initiated at the age of 14, but led to many related complications, including peritonitis, hypertensive retinopathy and encephalopathy, and acute heart failure. Initially, we were unaware of his developmental characteristics and autism spectrum disorder without intellectual disability, but through lengthy observations by various healthcare professionals, his unique characteristics were noticed. Because the patient often displayed a discrepancy between behavior and speech, we cautiously studied his thoughts and behaviors, and developed a special approach to ensure safe peritoneal dialysis.ConclusionsWhen many peritoneal dialysis-related complications occur in a patient with normal intelligence quotient, autism spectrum disorder should be considered as a possible cause.
    BMC, Mar. 2023, RENAL REPLACEMENT THERAPY, 9(1) (1), English
    Scientific journal

  • Eri Okada, Yuya Aoto, Tomoko Horinouchi, Tomohiko Yamamura, Yuta Ichikawa, Yu Tanaka, Chika Ueda, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, Ryota Suzuki, Joichi Usui, Kunihiro Yamagata, Kazumoto Iijima, Kandai Nozu
    BACKGROUND AND OBJECTIVES: The evident genotype-phenotype correlation shown by the X-linked Alport syndrome warrants the assessment of the impact of identified gene variants on aberrant splicing. We previously reported that single nucleotide variants (SNVs) in the last nucleotide of exons in COL4A5 cause aberrant splicing. It is known that the nucleotides located 2nd and 3rd to the last nucleotides of exons can also play an essential role in the first step of the splicing process. In this study, we aimed to investigate whether SNVs positioned 2nd or 3rd to the last nucleotide of exons in COL4A5 resulted in aberrant splicing. METHODS: We selected eight candidate variants: six from the Human Gene Variant Database Professional and two from our cohort. We performed an in-vitro splicing assay and reverse transcription-polymerase chain reaction (RT-PCR) for messenger RNA obtained from patients, if available. RESULTS: The candidate variants were initially classified into the following groups: three nonsense, two missense, and three synonymous variants. Splicing assays and RT-PCR for messenger RNA revealed that six of the eight variants caused aberrant splicing. Four variants, initially classified as non-truncating variants, were found to be truncating ones, which usually show relatively more severe phenotypes. CONCLUSION: We revealed that exonic SNVs positioned 2nd or 3rd to the last nucleotide of exons in the COL4A5 were responsible for aberrant splicing. The results of our study suggest that attention should be paid when interpreting the pathogenicity of exonic SNVs near the 5' splice site.
    Mar. 2023, Clinical and experimental nephrology, 27(3) (3), 218 - 226, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Zentaro Kiuchi, Kandai Nozu, Kunimasa Yan, Harald Jüppner
    Abstract Bartter syndrome type 1 is caused by mutations in the solute carrier family 12 member 1 (SLC12A1), encoding the sodium-potassium-chloride cotransporter-2 (NKCC2). In addition to causing renal salt-losing tubulopathy, SLC12A1 mutations are known to cause nephrocalcinosis due to hypercalciuria, as well as failure to thrive associated with abnormal calcium and phosphorus homeostasis. We report a now 7-year-old Japanese girl with polyuria, hyponatremia, hypokalemia, and metabolic alkalosis, in whom compound heterozygous novel SLC12A1 mutations were identified. Elevated parathyroid hormone (PTH) levels were consistently noted after the age of 1 year in conjunction with gradually declining serum calcium and increasing serum phosphorus levels. To confirm suspected PTH-resistance, Ellsworth Howard tests were performed at the ages of 6 years 8 months and 6 years 10 months in the absence or presence of ibuprofen, respectively. Urinary adenosine 3′,5′-cyclic monophosphate excretion increased on both occasions in response to PTH(1-34) infusion suggesting pseudohypoparathyroidism type II. However, only during treatment with ibuprofen did PTH induce an almost normal phosphaturic response. The nonsteroidal anti-inflammatory drugs thus enhanced growth velocity, alleviated hypercalciuria, and increased PTH-stimulated urinary phosphorus excretion without significantly affecting renal function.
    The Endocrine Society, Feb. 2023, JCEM Case Reports, 1(2) (2), English
    [Refereed]
    Scientific journal

  • Tomoko Horinouchi, Chika Ueda, Hideaki Kitakado, Norishige Yoshikawa, Kandai Nozu
    Feb. 2023, Journal of nephrology, 1 - 4, English, International magazine
    Scientific journal

  • Ruka Nakasone, Miki Ogi, Aoi Kawamura, Osamu Miyake, Takumi Kido, Shinya Abe, Naoto Takahashi, Kandai Nozu, Kazumichi Fujioka
    We report a case of vertical transmission of Coxsackievirus (CV)-A6 with severe congenital pneumonia/sepsis. A male infant presented with severe respiratory symptoms at birth and was treated with full cardiopulmonary support, including inhaled nitric oxide. Three days before delivery, his older brother was diagnosed with hand, foot, and mouth disease (HFMD). His mother developed transient fever 1 day before delivery and presented a blister on her thumb 2 days after delivery. A multiplex polymerase chain reaction test on day 2 was positive for human rhinovirus/enterovirus. CV-A6 was later detected in the serum, tracheal aspirate, and stool of the patient sampled on day 6, and in the maternal serum sampled on the day of delivery. He was diagnosed with congenital CV-A6 pneumonia/sepsis caused by vertical transmission, based on VP1 consensus sequences used for typing of the virus that demonstrated a 100% match between the mother and infant. Further, the strain was closely related to the lethal CV-A6-Changchun strains in the phylogenetic analysis of the P2 region, which contributes to the pathogenicity. In conclusion, congenital CV-A6 infection should be considered if a woman exhibits HFMD symptoms during the perinatal period. Detailed virologic examination is useful for understanding its pathogenesis.
    Feb. 2023, International journal of environmental research and public health, 20(4) (4), English, International magazine
    Link to Kobe Univ. Repository (Kernel)

  • AVPR2ヘテロ接合体バリアントを持つ女性における,X染色体不活性化パターンと腎性尿崩症の発症との相関
    鈴木 諒太, 岡田 絵里, 榊原 菜々, 大塚 泰史, 岡 政史, 西川 有希, 亀田 啓, 高橋 由華, 武者 育麻, 石森 真吾, 市川 裕太, 北角 英晶, 田中 悠, 近藤 淳, 堀之内 智子, 岡本 孝之, 野津 寛大
    (公社)日本小児科学会, Feb. 2023, 日本小児科学会雑誌, 127(2) (2), 204 - 204, Japanese

  • COL4A5遺伝子のイントロン+3から+5のバリアントにおける病原性の有無の検討
    北角 英晶, 青砥 悠哉, 市川 裕太, 田中 悠, 鈴木 諒太, 増田 知佳, 近藤 淳, 岡田 絵里, 榊原 菜々, 堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2023, 日本小児科学会雑誌, 127(2) (2), 251 - 251, Japanese

  • 非IgA型びまん性メサンギウム増殖発症の頻回再発型ネフローゼ症候群治療経過中にIgA腎症を発症した1例
    市川 裕太, 堀之内 智子, 田中 悠, 北角 英晶, 増田 知佳, 近藤 淳, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Feb. 2023, 日本小児科学会雑誌, 127(2) (2), 305 - 305, Japanese

  • 白井 佳祐, 芦名 満理子, 福田 拓弥, 鮫島 智大, 城戸 拓海, 阿部 真也, 野津 寛大, 藤岡 一路
    一絨毛膜一羊膜双胎第一子のみに発症した上衣下異所性灰白質の1例を経験したため報告する。症例は在胎30週3日,出生体重1,316g,一絨毛膜一羊膜(MM)双胎第一子の女児。出生時から頭部エコーで右側脳室拡大と壁不整を認め,日齢56の頭部MRI検査で上衣下異所性灰白質の診断となった。異所性灰白質の原因である先天性サイトメガロウイルス感染は尿ろ紙PCR検査で否定され,第二子に同様の頭部MRI異常を認めないことから遺伝的素因も否定的であり,MM双胎に起因する双胎間血流不均衡に伴う胎児期の脳血流異常が異所性灰白質発症の原因と推察した。(著者抄録)
    (株)総合医学社, Feb. 2023, 小児科臨床, 76(1) (1), 61 - 65, Japanese

  • Yuki Nakayama, Naoki Sawa, Tatsuya Suwabe, Masayuki Yamanouchi, Daisuke Ikuma, Hiroki Mizuno, Eiko Hasegawa, Junichi Hoshino, Akinari Sekine, Yuki Oba, Kei Kono, Keiichi Kinowaki, Kenichi Ohashi, Yutaka Yamaguchi, Kandai Nozu, Yoshifumi Ubara
    We evaluated kidney histology in a 43-year-old woman with autosomal dominant tubulointerstitial kidney disease subtype hepatocyte nuclear factor 1β. Magnetic resonance imaging showed multiple cysts in the renal medullary area, and computed tomography showed hypoplasia of the pancreatic body and tail. A kidney biopsy showed thinning of the cortex, size reduction of glomerular tuft area, proximal tubule clustering, fibrosis around the tubules, loss of peritubular capillaries, and multilayered epithelial cells of cortical collecting ducts; this last finding was consistent with so-called medullary dysplasia specific to congenital disease, in which the renal pelvic epithelial cells enter the collecting duct.
    Feb. 2023, Internal medicine (Tokyo, Japan), 62(3) (3), 419 - 422, English, Domestic magazine
    Scientific journal

  • 生後2ヵ月以内の症候性先天性サイトメガロウイルス感染症児を対象とした経口バルガンシクロビル治療 医師主導治験の結果
    森岡 一朗, 伊藤 嘉規, 吉川 哲史, 森内 浩幸, 高橋 尚人, 藤岡 一路, 野津 寛大, 児玉 知之, 筧 康正, 岡 明
    (公社)日本小児科学会, Feb. 2023, 日本小児科学会雑誌, 127(2) (2), 190 - 190, Japanese

  • Tsukasa Tanaka, Hiroshi Yamaguchi, Yusuke Ishida, Kazumi Tomioka, Masahiro Nishiyama, Daisaku Toyoshima, Azusa Maruyama, Hiroki Takeda, Hiroshi Kurosawa, Ryojiro Tanaka, Kandai Nozu, Hiroaki Nagase
    BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.
    Jan. 2023, BMC neurology, 23(1) (1), 28 - 28, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kazumi Tomioka, Masahiro Nishiyama, Shoichi Tokumoto, Hiroshi Yamaguchi, Kazunori Aoki, Yusuke Seino, Daisaku Toyoshima, Hiroshi Kurosawa, Hiroko Tada, Hiroshi Sakuma, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima, Hiroaki Nagase
    BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1β, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1β, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.
    Jan. 2023, BMC neurology, 23(1) (1), 7 - 7, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 市川 裕太, 榊原 菜々, 田中 悠, 上田 知佳, 北角 英晶, 近藤 淳, 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, 2023, 日本小児腎臓病学会雑誌, 36, 53 - 53, Japanese

  • 田中 悠, 堀之内 智子, 市川 裕太, 上田 知佳, 北角 英晶, 近藤 淳, 榊原 菜々, 吉川 徳茂, 森貞 直哉, 野津 寛大
    (一社)日本小児腎臓病学会, 2023, 日本小児腎臓病学会雑誌, 36, 53 - 54, Japanese

  • 上杉 裕紀, 井上 翔太郎, 今川 幸人, 西村 明紘, 中谷 尚子, 二野 菜々子, 田村 彰広, 山本 暢之, 西村 範行, 野津 寛大
    グルコース6リン酸脱水素酵素(G6PD)欠損症は赤血球酵素異常の中で最も頻度が高く,世界で4億人の患者がいるとされるが本邦での有病率は0.1%未満と少ない。感染症や特定の薬剤投与での酸化ストレスにより溶血発作が生じる。症例は当院でフォロー中のG6PD欠損症の18歳男性で,受診2日前から発熱し,受診当日の朝,排尿中に意識消失し自宅で倒れているところを発見され当院に救急搬送された。SARS-CoV-2陽性,Hgb6.6g/dL,LDH 1,894U/L,ハプトグロビン7mg/dLからCOVID-19に伴う溶血発作と診断し赤血球輸血を行った。輸血後全身状態は改善するも,その後も貧血は進行し解熱するまでの間に計6単位の赤血球輸血を要した。我々が知る限り,本症例が本邦でCOVID-19を契機に溶血発作を生じた初の報告である。G6PD欠損症患者は溶血発作,血栓傾向など重症化リスクが高いためCOVID-19発症時には慎重な対応が重要である。(著者抄録)
    兵庫県小児科医会, 2023, 兵庫県小児科医会報, (79) (79), 13 - 17, Japanese

  • Hiroaki Nagase, Hiroshi Yamaguchi, Shoichi Tokumoto, Yusuke Ishida, Kazumi Tomioka, Masahiro Nishiyama, Kandai Nozu, Azusa Maruyama
    Our goal was to conduct a scoping review of the literature on the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy in children, focusing on treatment targets and treatment initiation timing. We performed literature searches using PubMed for articles reporting treatments of infection-triggered encephalopathy syndrome/acute encephalopathy. We included articles describing specific treatments for acute encephalopathy with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series studies without control groups in this review, if the studies contained at least two cases with clear treatment goals. Therapies were classified based on their mechanisms of action into brain protection therapy, immunotherapy, and other therapies. We operationally categorized the timing of treatment initiation as T1 (6-12 h), T2 (12-24 h), T3 (24-48 h), and T4 (>48 h) after the onset of seizures and/or impaired consciousness. Thirty articles were included in this review; no randomized control study was found. Eleven retrospective/historical cohort studies and five case-control studies included control groups with or without specific therapies or outcomes. The targeted conditions and treatment timing varied widely across studies. However, the following three points were suggested to be effective in multiple studies: (1) Careful seizure management and targeted temperature management within 12 h (T1) of onset of febrile seizure/prolonged impaired consciousness without multiple organ failure may reduce the development of acute encephalopathy with biphasic seizures and late reduced diffusion; (2) immunotherapy using corticosteroids, tocilizumab, or plasma exchange within 24 h (T1-T2) of onset of acute necrotizing encephalopathy may reduce sequelae; and (3) anakinra therapy and ketogenic diet demonstrate little evidence of neurologic sequelae reduction, but may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks (T4) after onset in children with febrile infection-related epilepsy syndrome. Although available studies have no solid evidence in the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy, this scoping review lays the groundwork for future prospective clinical trials.
    2023, Frontiers in neuroscience, 17, 1150868 - 1150868, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yukino Kawanami, Tomoko Horinouchi, Naoya Morisada, Takeshi Kato, Kandai Nozu
    We encountered a case with congenital iris coloboma, omphalocele, and developmental delay with a 2.5 Mb deletion on chromosome 4q25 encompassing PITX2, leading to Axenfeld-Rieger syndrome (ARS), NEUROG2, and ANK2. ARS is characterized by the aplasia of the anterior eye, odontogenesis, and abdominal wall aplasia. In our case, iris coloboma and omphalocele were thought to be caused by PITX2 haploinsufficiency. However, these symptoms are nonspecific, and clinical symptoms alone can make it difficult to make a correct diagnosis. In addition, the genes responsible for developmental delay, among others, are not well understood. Developmental delay, in this case, might be caused due to NEUROG2 haploinsufficiency. In spite of the partial deletion of ANK2, the causative gene of long QT syndrome type 4, the electrocardiogram was normal. Genetic testing can lead to a correct diagnosis, and it may be effective in detecting complications.
    2023, Case reports in genetics, 2023, 4592114 - 4592114, English, International magazine
    Link to Kobe Univ. Repository (Kernel)

  • Shingo Ishimori, Tomoko Horinouchi, Junya Fujimura, Tomohiko Yamamura, Natsuki Matsunoshita, Naohiro Kamiyoshi, Mai Sato, Masao Ogura, Koichi Kamei, Kenji Ishikura, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Prospective research of children receiving heterogeneous vaccines has shown that immunization is not associated with pediatric idiopathic nephrotic syndrome (NS) relapses. However, prospective data concentrating only on influenza (flu) virus vaccines are not available. METHODS: This multicenter prospective study was conducted in children with NS who received inactivated flu vaccines from June 2017 to July 2018. The day of flu vaccination was defined as day 0, and the period between prevaccination and postvaccination days was defined as - X to + Y (period from day - 180 to 0 as the precontrolled period). The primary outcome was the NS relapse rate from day 0 to + 30 as a direct association with vaccination compared with those in the precontrolled period. Exacerbation was defined as children experiencing more NS relapses after vaccination compared with those in the precontrolled period, or children starting any new immunosuppressants due to NS relapse after vaccination. RESULTS: Sixty-three children were included. Relapse rates were not significantly different between the precontrolled period and 0 to + 30 periods (0.38 vs. 0.19 times/person-year, p = 0.95). Although the exacerbation rate during the 0 to + 180 period in children without NS relapse in the precontrolled period was very low (4/54 [7.4 %]), children with at least one NS relapse in the precontrolled period showed a remarkable increase in the rate (4/9 [44.4%]; p = 0.01). CONCLUSIONS: Flu vaccination did not significantly precipitate the direct relapse of NS in children. However, it might increase the disease activity in children with at least one NS relapse within a half year before vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.
    Nov. 2022, Pediatric nephrology (Berlin, Germany), 38(7) (7), 1 - 10, English, International magazine
    Scientific journal

  • Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hiroyuki Awano
    Spinal muscular atrophy (SMA) is a common devastating neuromuscular disorder, usually involving homozygous deletion of the SMN1 gene. Newly developed drugs can improve the motor functions of infants with SMA when treated in the early stage. To ensure early diagnosis, newborn screening for SMA (SMA-NBS) via PCR-based genetic testing with dried blood spots (DBSs) has been spreading throughout Japan. In Hyogo Prefecture, we performed a pilot study of SMA-NBS to assess newborn infants who underwent routine newborn metabolic screening between February 2021 and August 2022. Hyogo Prefecture has ~40,000 live births per year and the estimated incidence of SMA is 1 in 20,000-25,000 based on genetic testing of symptomatic patients with SMA. Here, we screened 8336 newborns and 12 screen-positive cases were detected by real-time PCR assay. Multiplex ligation-dependent probe amplification assay excluded ten false positives and identified two patients. These false positives might be related to the use of heparinized and/or diluted blood in the DBS sample. Both patients carried two copies of SMN2, one was asymptomatic and the other was symptomatic at the time of diagnosis. SMA-NBS enables us to prevent delayed diagnosis of SMA, even if it does not always allow treatment in the pre-symptomatic stage.
    Nov. 2022, Genes, 13(11) (11), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 増田 知佳, 堀之内 智子, 北角 英晶, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 野津 寛大
    (一社)日本小児腎臓病学会, Nov. 2022, 日本小児腎臓病学会雑誌, 35(2) (2), 167 - 167, Japanese

  • 近藤 淳, 長野 智那, 北角 英晶, 増田 知佳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 佐々木 聡, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, Nov. 2022, 日本小児腎臓病学会雑誌, 35(2) (2), 159 - 159, Japanese

  • 大竹 結衣, 貝藤 裕史, 森貞 直哉, 矢谷 和也, 稲熊 洋祐, 野津 寛大, 杉多 良文, 田中 亮二郎, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2022, 日本小児腎臓病学会雑誌, 35(2) (2), 170 - 170, Japanese

  • Hiroshi Yamaguchi, Kandai Nozu, Hiroaki Hanafusa, Yoshinori Nambu, Takumi Kido, Atsushi Kondo, Akihiro Tamura, Hiroyuki Awano, Ichiro Morioka, Hiroaki Nagase, Akihito Ishida
    Rotavirus (RV) is the leading cause of acute gastroenteritis (AGE), particularly in infants. In 2006, the high efficacy of oral RV vaccines (RVVs, RotarixTM and RotaTeqTM) was demonstrated. Voluntary RVV started in Japan in 2011, and in October 2020 were launched as universal oral RVVs in Japan. However, the impact of changes from voluntary to universal RVVs has not been studied in a primary emergency medical center in Japan. We investigated changes in the number of pediatric patients with AGE after introducing universal RVVs in our center. A clinical database of consecutive patients aged <16 who presented to Kobe Children's Primary Emergency Medical Center between 1 April 2016 and 30 June 2022 was reviewed. After implementing universal RVVs, fewer children presented with RV-associated AGE (the reduction of proportion of the patients in 2022 was -61.7% (all ages), -57.9% (<1 years), -67.8% (1-<3 years), and -61.4% (3-<5 years) compared to 2019). A similar decrease in those of age who were not covered by the universal RVV was observed. There was a significant decline in the number of patients with AGE during the RV season who presented to the emergency department after implementing universal RVVs.
    Oct. 2022, Vaccines, 10(11) (11), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroaki Hanafusa, Shinya Abe, Shohei Ohyama, Yuki Kyono, Takumi Kido, Ruka Nakasone, Mariko Ashina, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka
    BACKGROUND: Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two UGT1A1 genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between UGT1A1 variants and Bf levels in newborns has not been elucidated. METHODS: We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two UGT1A1 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, n = 77) and a non-high Bf group (Bf < 1.0 µg/dL, n = 407), based on the peak Bf values. Logistic regression analysis was performed to calculate the odds ratios (ORs) for each variant allele compared to wild-type alleles. RESULTS: The frequencies of the A allele in rs4148323 and (TA)7 allele in rs3064744 in the high Bf group (29% and 4%, respectively) were significantly different from those in the non-high Bf group (16% and 12%, respectively). In logistic regression analysis, for rs4148323, the A allele was significantly associated with an increased risk of hyper-free bilirubinemia over the G allele (adjusted OR: 1.80, 95% confidence interval [CI]: 1.19-2.72, p < 0.01). However, for rs3064744, the (TA)7 allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA)6 allele (adjusted OR: 0.42, 95% CI: 0.18-0.95, p = 0.04). CONCLUSIONS: This study is the first to show that the A allele in rs4148323 is a risk factor and that the (TA)7 allele in rs3064744 is a protective factor for developing hyper-free bilirubinemia in Japanese newborns.
    Oct. 2022, International journal of environmental research and public health, 19(20) (20), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 活性型Rac1蛋白の定量解析により診断した新規ARHGAP24遺伝子変異による小児巣状分節性糸球体硬化症の1例
    近藤 淳, 増田 知佳, 北角 英晶, 榊原 菜々, 堀之内 智子, 佐々木 聡, 野津 寛大
    (一社)日本腎臓学会, Oct. 2022, 日本腎臓学会誌, 64(6-W) (6-W), 714 - 714, Japanese

  • 濃厚な家族歴があり,両側多発腎嚢胞・肝膵嚢胞を有するAlport症候群の一例
    杉本 悠, 中田 絋介, 横井 秀基, 松原 雄, 野津 寛大, 柳田 素子
    (一社)日本腎臓学会, Oct. 2022, 日本腎臓学会誌, 64(6-W) (6-W), 731 - 731, Japanese

  • 市川 裕太, 藤岡 一路, 福田 拓弥, 川村 あおい, 鮫島 智大, 城戸 拓海, 仲宗根 瑠花, 阿部 真也, 芦名 満理子, 野津 寛大
    【背景】偽性低アルドステロン症(pseudohypoaldosteronism,PHA)は,新生児期の病像および頻度が不明である。本検討では過去に国内で報告された新生児PHAについて網羅的に文献レビューを行った。【方法】医学中央雑誌で,1970～2019年の期間にキーワード「新生児」かつ「偽性低アルドステロン症」を満たす文献を収集し,内容から病像を検討した。【結果】当該期間に文献的に報告された新生児PHAは75例であり,その内訳は,原発性29例,続発性23例,明らかな原因なし8例,原因記載なし15例であり,在胎週数の中央値は38(25～42)週であった。87%は何らかの初発症状を認めたが,13%は無症状例であった。発症時検査所見はNa:中央値124(103～136)mEq/L,K:中央値6.9(4.2～11.5)mEq/Lであった。【結論】新生児PHAでは,原発性および続発性に分類されない「明らかな原因なし」のいわゆる「特発性」と思われる症例が存在する。新生児で低Na高K血症を認めた際は本症の可能性を考慮する必要がある。(著者抄録)
    (株)総合医学社, Oct. 2022, 小児科臨床, 75(5) (5), 773 - 793, Japanese

  • 死亡時のアシルカルニチン分析結果を契機に確定診断したグルタル酸血症2型の一例
    坊 亮輔, 池谷 紀衣子, 花房 宏昭, 南部 静紀, 奥谷 貴弘, 野津 寛大, 粟野 宏之
    (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 193 - 193, Japanese

  • Nanako Nino, Toshiaki Ishida, Naoko Nakatani, Kyaw San Lin, Kaung Htet Nay Win, Cho Yee Mon, Akihiro Nishimura, Shotaro Inoue, Akihiro Tamura, Nobuyuki Yamamoto, Suguru Uemura, Atsuro Saito, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Kandai Nozu, Noriyuki Nishimura
    More than half of high-risk neuroblastoma (NB) patients have experienced relapse due to the activation of chemoresistant minimal residual disease (MRD) even though they are treated by high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although MRD in high-risk NB patients can be evaluated by quantitative PCR with several sets of neuroblastoma-associated mRNAs (NB-mRNAs), the prognostic significance of MRD in PBSC grafts (PBSC-MRD) is unclear. In the present study, we collected 20 PBSC grafts from 20 high-risk NB patients and evaluated PBSC-MRD detected by droplet digital PCR (ddPCR) with 7NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNA). PBSC-MRD in 11 relapsed patients was significantly higher than that in 9 non-relapsed patients. Patients with a higher PBSC-MRD had a lower 3-year event-free survival (P = 0.0148). The present study suggests that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a prognostic impact on high-risk NB patients.
    Oct. 2022, Heliyon, 8(10) (10), e10978, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Chieko Matsumura, Katsuyoshi Kanemoto, Yuichi Uno, Masayo Kobayashi, Mai Masuda, Toshiyuki Imasawa, Masataka Hisano, Sumie Homma, Masataka Honda, Kandai Nozu, Junichi Yamaguchi
    BACKGROUND: Urinary screening for 3-year-olds cannot adequately detect congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: Urinary screening for 3-year-olds was investigated over 30 years. Dipsticks for proteinuria, hematuria, glycosuria, leukocyturia, and nitrite at first screening, and dipsticks, urinary sediments, and renal ultrasonography at second screening were performed. Screening results were evaluated. RESULTS: The positive rates of proteinuria, hematuria, leukocyturia, and nitrite relative to 218,831 children at the first screening were 1.0%, 4.6%, 2.3%, and 0.88%, respectively. Thirty-seven glomerular disease, 122 CAKUT, and 5 urological disease cases were found. We detected 6 stage 3-4 chronic kidney disease (CKD) and 3 end-stage kidney disease cases, including 3 CAKUT, comprising 2 bilateral renal hypoplasia and 1 vesicoureteral reflux (VUR), and 6 glomerular diseases, comprising 4 focal segmental glomerulosclerosis and 2 Alport syndrome. The positive rates relative to 218,831 children and CKD detection rates for each tentative diagnosis of mild hematuria, severe hematuria, proteinuria and hematuria, proteinuria, and suspected urinary tract infection were 1.4% and 0.67%, 0.11% and 3.7%, 0.01% and 28.6%, 0.02% and 45.0%, and 0.08% and 9.7%, respectively. Among 14 VUR cases with significant bacteriuria, 13 were found by leukocyturia, 12 had grade ≥ IV VUR, and 10 had severe renal scars. CONCLUSIONS: Nine stage 3-5 CKD cases comprising 3 CAKUT and 6 glomerular disease were found by urinary screening of 3-year-olds among 218,831 children. The combination of urine dipsticks including leukocyturia at the first screening and ultrasonography at the second screening appeared useful.
    Sep. 2022, Clinical and experimental nephrology, English, Domestic magazine
    Scientific journal

  • Rini Rossanti, Tomoko Horinouchi, Nana Sakakibara, Tomohiko Yamamura, China Nagano, Shinya Ishiko, Yuya Aoto, Atsushi Kondo, Sadayuki Nagai, Hiroyuki Awano, Hiroaki Nagase, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    Gitelman syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by loss of function in the SLC12A3 gene (NM_000339.2), which encodes the natrium chloride cotransporter. The detection of homozygous or compound heterozygous SLC12A3 variants is expected in GS, but 18%-40% of patients with clinical GS carry only one mutant allele. Previous reports identified some pathogenic deep intronic variants in SLC12A3. Here, we report the screening of SLC12A3 deep intronic variants in 13 patients with suspected GS carrying one mutated SLC12A3 allele. Variant screening used the HaloPlex Target Enrichment System Kit capturing whole introns and the promotor region of SLC12A3, followed by SureCall variant analysis. Rare intronic variants (<1% frequency) were identified, and pathogenicity evaluated by the minigene system. Deep intronic variant screening detected seven rare SLC12A3 variants from six patients. Only one variant showed pathogenicity in the minigene system (c.602-16G>A, intron 4) through activation of a cryptic acceptor site. No variants were detected in the promotor region. Deep intronic screening identified only one pathogenic variant in patients with suspected GS carrying monoallelic SLC12A3 variants. Our results suggest that deep intronic variants partially explain the cause of monoallelic variants in patients with GS.
    Sep. 2022, American journal of medical genetics. Part A, 188(9) (9), 2576 - 2583, English, International magazine
    Scientific journal

  • Kazumichi Fujioka, Ruka Nakasone, Kosuke Nishida, Mariko Ashina, Itsuko Sato, Kandai Nozu
    (1) Background: Pseudohypoaldosteronism type 1 (PHA-1) is a disorder caused by renal tubular resistance to aldosterone and is characterized by problems with sodium regulation. PHA-1 is typically divided into primary PHA-1, which is caused by genetic mutation, and secondary PHA-1, which is associated with urinary tract abnormality. However, data on the clinical features of PHA-1 among newborn infants are limited. (2) Methods: We conducted a nationwide prospective surveillance study of neonatal PHA in Japan from 1 April 2019 to 31 March 2022 as part of a rare disease surveillance project of the Japan Society for Neonatal Health and Development. (3) Results: Fifteen cases (male:female = 7:8), including four primary, four secondary, and seven non-classified cases, were reported during the study period. The median gestational age and birthweight were 34 weeks (28-41) and 1852 g (516-4610), respectively. At the onset, the median serum Na and K levels were 132 mEq/L (117-137) and 6.3 mEq/L (4.7-8.3), respectively. The median plasma renin activity was 45 ng/mL/h (3.1-310, n = 9), active renin concentration was 1017 pg/mL (123-2909, n = 6), and serum aldosterone concentration was 5310 pg/mL (3250-43,700). (4) Conclusions: Neonatal PHA-1 was more common among preterm infants with no male predominance. It developed immediately after birth in cases without genetic or renal complications.
    Aug. 2022, Journal of clinical medicine, 11(17) (17), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • China Nagano, Shigeo Hara, Norishige Yoshikawa, Asami Takeda, Yoshimitsu Gotoh, Riku Hamada, Kentaro Matsuoka, Masaki Yamamoto, Shuichiro Fujinaga, Koji Sakuraya, Koichi Kamei, Yuko Hamasaki, Hideyo Oguchi, Yoshinori Araki, Yayoi Ogawa, Takayuki Okamoto, Shuichi Ito, Seiji Tanaka, Hiroshi Kaito, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, Tomoko Horinouchi, Tomohiko Yamamura, Hiroaki Nagase, Kazumoto Iijima, Kandai Nozu
    Background: Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients. Methods: This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates. Results: The distribution of histologic variants according to the Columbia classification was 45% (n=53) FSGS not otherwise specified, 21% (n=25) cellular, 15% (n=18) perihilar, 13% (n=16) collapsing, and 6% (n=7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P<0.001). Conclusions: We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS.
    Aug. 2022, Kidney360, 3(8) (8), 1384 - 1393, English, International magazine
    Scientific journal

  • てんかん重積状態・急性脳症における疾患原因遺伝子の同定の試み
    山口 宏, 花房 宏昭, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗
    (一社)日本てんかん学会, Aug. 2022, てんかん研究, 40(2) (2), 410 - 410, Japanese

  • 近藤 淳, 堀之内 智子, 山村 智彦, 増田 知佳, 北角 英昌, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 吉川 徳茂, 野津 寛大
    背景:ステロイド抵抗性ネフローゼ症候群(steroid resistance nephrotic syndrome:SRNS)の約30%はpodocyte関連遺伝子の病的変異により発症し,これらの症例では免疫抑制療法への反応性が乏しいことが報告されている。症例1:1歳男児。特発性ネフローゼ症候群に対してステロイド治療が開始されたが奏効せず,SRNSと診断された。浮腫が目立たず,乳児期より感冒の度に眼瞼浮腫を認めていたことが判明し,遺伝性ネフローゼ症候群が強く疑われた。遺伝学的検査でNPHS1遺伝子に複合ヘテロ接合体変異が同定され,遺伝子変異に伴うSRNSと診断された。免疫抑制療法の中止とACE阻害薬が開始され,発症後2年時点で高度蛋白尿と低アルブミン血症は持続しているが,浮腫の増悪や腎機能低下は認めていない。結論:非典型的な経過や身体所見から遺伝子変異の関与が疑われる症例では,遺伝学的検査を積極的に行うことが治療方針の決定に有用である。(著者抄録)
    日本小児腎不全学会, Aug. 2022, 日本小児腎不全学会雑誌, 42, 97 - 100, Japanese

  • 坊 亮輔, 李 知子, 上田 雅章, 野津 寛大, 竹島 泰弘, 飯島 一誠, 粟野 宏之
    (一社)日本マススクリーニング学会, Aug. 2022, 日本マス・スクリーニング学会誌, 32(2) (2), 233 - 233, Japanese

  • 福山型筋ジストロフィーのエラストグラフィーを用いた骨格筋画像評価
    池田 真理子, 原田 理沙, 長坂 美和子, 粟野 宏之, 酒井 良忠, 野津 寛大, 戸田 達史
    (一社)日本筋学会, Aug. 2022, 日本筋学会学術集会プログラム・抄録集, 8回, 120 - 120, Japanese

  • 早期の遺伝学的検査が治療方針選択に有用であったステロイド抵抗性ネフローゼ症候群の1例
    近藤 淳, 堀之内 智子, 山村 智彦, 増田 知佳, 北角 英昌, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 吉川 徳茂, 野津 寛大
    背景:ステロイド抵抗性ネフローゼ症候群(steroid resistance nephrotic syndrome:SRNS)の約30%はpodocyte関連遺伝子の病的変異により発症し,これらの症例では免疫抑制療法への反応性が乏しいことが報告されている。症例1:1歳男児。特発性ネフローゼ症候群に対してステロイド治療が開始されたが奏効せず,SRNSと診断された。浮腫が目立たず,乳児期より感冒の度に眼瞼浮腫を認めていたことが判明し,遺伝性ネフローゼ症候群が強く疑われた。遺伝学的検査でNPHS1遺伝子に複合ヘテロ接合体変異が同定され,遺伝子変異に伴うSRNSと診断された。免疫抑制療法の中止とACE阻害薬が開始され,発症後2年時点で高度蛋白尿と低アルブミン血症は持続しているが,浮腫の増悪や腎機能低下は認めていない。結論:非典型的な経過や身体所見から遺伝子変異の関与が疑われる症例では,遺伝学的検査を積極的に行うことが治療方針の決定に有用である。(著者抄録)
    日本小児腎不全学会, Aug. 2022, 日本小児腎不全学会雑誌, 42, 97 - 100, Japanese

  • Hideaki Kitakado, Tomoko Horinouchi, Chika Masuda, Atsushi Kondo, Sadayuki Nagai, Yuya Aoto, Nana Sakakibara, Takeshi Ninchoji, Norishige Yoshikawa, Kandai Nozu
    BACKGROUND: Oligomeganephronia (OMN) is a rare congenital anomaly involving the kidney and urinary tract, characterized by decreased number and compensatory hypertrophy of the nephron. It is caused by abnormal kidney development during the embryonic period, especially in patients with low birth weight; however, the actual etiology and clinical features remain unknown. We aim to reveal the clinical and pathological characteristics, treatment, and outcome. METHODS: Ten patients diagnosed with OMN between 2013 and 2020 were retrospectively investigated. The data were presented as the median ± interquartile range, and statistical significance was set at p < 0.05. RESULTS: The age at diagnosis was 14.1 years, the male-to-female ratio was 6:4, and only four cases were born with low birth weight. The estimated glomerular filtration rate (eGFR) was 62.2 mL/min/1.73 m2. The glomerulus diameter of OMN patients was significantly larger (217 vs. 154 µm, p < 0.001) in OMN patients, and the number of glomeruli of OMN patients was lower (0.89 vs. 2.05/mm2, p < 0.001) than the control group. Eight of the ten cases were identified by urinary screening. Nine patients were treated with renin-angiotensin system (RAS) inhibitors, following which proteinuria successfully decreased or disappeared. Their median eGFR was also stable, 53.3 mL/min/1.73 m2. CONCLUSIONS: As few symptoms can lead to OMN discovery, most patients were found during urine screening at school. Kidney dysfunction was observed in all patients at the time of kidney biopsy. Proteinuria has been significantly reduced and the decline rate of eGFR might be improved by RAS inhibitors. "A higher resolution version of the Graphical abstract is available as Supplementary information".
    Jul. 2022, Pediatric nephrology (Berlin, Germany), 38(3) (3), 757 - 762, English, International magazine
    Scientific journal

  • Ichiro Morioka, Yasumasa Kakei, Takashi Omori, Kandai Nozu, Kazumichi Fujioka, Naoto Takahashi, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Akira Oka
    Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was -246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.
    Jun. 2022, Journal of clinical medicine, 11(13) (13), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 【ポドサイトパチー】ポドサイト疾患の遺伝学的要因 遺伝性ポドサイト疾患とそのリスク因子
    青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 野津 寛大
    (有)科学評論社, Jun. 2022, 腎臓内科, 15(6) (6), 633 - 643, Japanese

  • Yuya Aoto, Takeshi Ninchoji, Hiroshi Kaito, Yuko Shima, Junya Fujimura, Naohiro Kamiyoshi, Shingo Ishimori, Koichi Nakanishi, Shogo Minamikawa, Shinya Ishiko, Nana Sakakibara, China Nagano, Tomoko Horinouchi, Tomohiko Yamamura, Sadayuki Nagai, Atsushi Kondo, Yosuke Inaguma, Ryojiro Tanaka, Norishige Yoshikawa, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Patients with immunoglobulin A nephropathy who present with focal mesangial proliferation (focal IgAN) can have a relatively good prognosis, and renin-angiotensin system inhibitor (RAS-i) is commonly used as the initial treatment. However, there are some complicated focal IgAN cases with resistance to RAS-i treatment or nephrotic-range proteinuria. Thus, combination therapy including corticosteroids is often used. This study aimed to evaluate the efficacy of combination therapy for complicated focal IgAN cases by comparing to diffuse mesangial proliferation (diffuse IgAN). METHODS: We conducted a multicenter retrospective study on 88 children who received 2-year combination therapy. The participants were classified based on pathological severity: focal IgAN (n = 26) and diffuse IgAN (n = 62). RESULTS: In total, 26 patients with focal IgAN and 52 with diffuse IgAN achieved proteinuria disappearance within 2 years (100 vs. 83.9%, P = 0.03). Moreover, the time to proteinuria disappearance was significantly shorter in the focal IgAN group than in the diffuse IgAN group (2.9 vs. 4.2 months, P < 0.01) and all patients with focal IgAN achieved proteinuria disappearance within 8 months. At the last observation (8.6 vs. 10.4 years, P = 0.13), only patients with diffuse IgAN (n = 12) had greater than stage 2 chronic kidney disease. In terms of irreversible adverse events, one patient exhibited cataracts. CONCLUSION: Combination therapy was significantly effective in patients with complicated focal IgAN. Moreover, the long-term prognosis was good, and the duration of combination therapy for complicated focal IgAN can be decreased to reduce adverse events.
    Jun. 2022, Clinical and experimental nephrology, 26(6) (6), 561 - 570, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Harada R, Taniguchi-Ikeda M, Nagasaka M, Tatsiuya Nishii, Atsuyuki Inui, Tetsushi Yamamoto, Ichiro Morioka, Ryosuke Kuroda, Kazumoto Iijima, Kandai Nozu, Yoshitada Sakai, Tatsushi Toda
    May 2022, Neuromuscular Disorders
    Link to Kobe Univ. Repository (Kernel)

  • Shutaro Suga, Yuki Kyono, Takumi Kido, Ruka Nakasone, Shinya Abe, Mariko Ashina, Kandai Nozu, Kazumichi Fujioka
    Although preterm infant mortality is low, the proportion of patients with treatment-requiring retinopathy of prematurity (TR-ROP) is high in Japan. Various multicenter studies have reported the risk factors for TR-ROP; however, no large-scale studies have been conducted in Japan. We retrospectively analyzed 13,645 infants born at < 28 weeks' gestation (January 1, 2009-December 31, 2018), and registered in the Neonatal Research Network of Japan database. TR-ROP was defined as ROP requiring retinal laser photocoagulation and/or intravitreal anti-vasoendothelial growth factor drugs. Multivariable logistic regression analysis was performed to identify factors associated with TR-ROP development. The median gestational age of enrolled infants was 26 weeks (interquartile range [IQR], 24-27 weeks), median birth weight was 760 g (IQR, 620-918 g). Proportion of patients with TR-ROP was 30.3%. TR-ROP was significantly associated with birth at < 26 weeks' gestational age (adjusted odds ratio [aOR] 1.54), blood transfusion (aOR 1.49), invasive ventilation ≥ 28 days (aOR 1.41), sepsis (aOR 1.29), birth weight < 750 g (aOR 1.28), intraventricular hemorrhage (aOR 1.33), delayed achievement of full enteral feeding > 14 days (aOR 1.28), and continuous positive airway pressure (CPAP) therapy ≥ 28 days (aOR 0.79). Supplemental oxygen ≥ 28 days was not associated with TR-ROP development. Lower gestational age at birth and birth weight, blood transfusion, prolonged invasive ventilation, sepsis, intraventricular hemorrhage, and delayed achievement of full enteral feeding were risk factors for TR-ROP, whereas CPAP use was protective against TR-ROP.
    May 2022, Scientific reports, 12(1) (1), 7799 - 7799, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 京野 由紀, 西山 将広, 徳元 翔一, 山口 宏, 冨岡 和美, 三品 浩基, 野津 寛大, 永瀬 裕朗
    (公社)日本小児保健協会, May 2022, 小児保健研究, 81(講演集) (講演集), 152 - 152, Japanese

  • 徳元 翔一, 西山 将広, 上田 拓耶, 本郷 裕斗, 山口 宏, 石田 悠介, 冨岡 和美, 豊嶋 大作, 丸山 あずさ, 野津 寛大, 石田 明人, 永瀬 裕朗
    (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S251 - S251, Japanese

  • 山口 宏, 西山 将広, 上田 拓耶, 本郷 裕斗, 徳元 翔一, 石田 悠介, 冨岡 和美, 豊嶋 大作, 中川 卓, 高見 勇一, 黒澤 寛史, 丸山 あずさ, 野津 寛大, 永瀬 裕朗
    (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S252 - S252, Japanese

  • 冨岡 和美, 永瀬 裕朗, 徳元 翔一, 山口 宏, 西山 将広, 岡田 由香, 野津 寛大
    (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S317 - S317, Japanese

  • 北角 英晶, 堀之内 智子, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 野津 寛大
    家族性中枢性尿崩症は緩徐進行性にバソプレシン(AVP)の分泌が低下し、多飲多尿を呈する常染色体顕性遺伝疾患である。AVP遺伝子の異常により変異蛋白が蓄積し、それによる小胞体ストレスが徐々にニューロン死を惹起すると考えられている。症例は14歳男児で、頭痛を主訴に来院した。家族歴として、母・母方祖母が中枢性尿崩症と診断されていた。児は弟と共に多飲多尿の症状を認めていたが、家族と同症状のため医療機関を受診していなかった。1日尿量6000mL、血清Na 139mEq/L、尿浸透圧58mOsm/kgで頭部MRIでは下垂体後葉の高信号が消失していた。デスモプレシン酢酸塩水和物投与後、尿浸透圧は493mOsm/kgまで上昇した。AVP遺伝子の検索を行ったところ、本人・母・弟にAVP遺伝子(NM_000490.5)の既報ヘテロ接合体変異(c.55G>A、p.Ala19Thr)を認め、AVP遺伝子異常に基づく中枢性尿崩症と確定診断した。家族性中枢性尿崩症家系では、家人も同様の症状を呈し、早期に医療機関の受診に至らないケースも多い。睡眠不足や日常生活のQOL改善、多飲多尿による水腎症・巨大膀胱の予防のためには早期診断・早期治療が有用で、その診断に遺伝学的検査が重要であった。(著者抄録)
    日本小児体液研究会, May 2022, 日本小児体液研究会誌, 14, 43 - 46, Japanese

  • 遺伝子診断の臨床応用 Alport症候群
    堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 180 - 180, Japanese

  • OCRL遺伝子splicing異常による疾患発症メカニズムの検討
    榊原 菜々, ロサンティ・リニ, 岡田 絵里, 近藤 淳, 永井 貞之, 青砥 悠哉, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 219 - 219, Japanese

  • 当院小児科の腎疾患患者の新型コロナウイルスワクチン接種状況
    北角 英晶, 堀之内 智子, 増田 知佳, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 忍頂寺 毅史, 野津 寛大
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 231 - 231, Japanese

  • COL4A5遺伝子エクソン内3'末端から2・3番目の一塩基置換は高率にスプライシング異常を来す
    岡田 絵里, 青砥 悠哉, 堀之内 智子, 榊原 菜々, 臼井 丈一, 山縣 邦弘, 野津 寛大
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 231 - 231, Japanese

  • Alport症候群モデルマウスにおけるエクソンスキッピング療法の信頼性保証試験成績報告
    青砥 悠哉, 山村 智彦, 堀之内 智子, 近藤 淳, 永井 貞之, 岡田 絵里, 榊原 菜々, 野津 寛大
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 231 - 231, Japanese

  • ステロイド感受性ネフローゼ症候群初発時にはSwitched memory B細胞の増加を認める
    永井 貞之, 藤村 順也, 忍頂寺 毅史, 石森 真吾, 神吉 直宙, 貝藤 裕史, 島 友子, 飯島 一誠, 野津 寛大, 堀之内 智子, 青砥 悠哉, 近藤 淳, 榊原 菜々, 増田 知佳, 北角 英晶
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 242 - 242, Japanese

  • 南部 静紀, 坊 亮輔, 徳元 翔一, 山口 宏, 冨岡 和美, 西山 将広, 永瀬 裕朗, 西尾 久英, 野津 寛大, 粟野 宏之
    (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S210 - S210, Japanese

  • 【腎臓とミトコンドリア】他の疾患と思われていたがミトコンドリア病であった症例
    渡邉 駿, 水野 裕基, 星野 純一, 澤 直樹, 中村 有紀, 石井 保夫, 土谷 良樹, 野津 寛大, 大橋 健一, 金綱 友木子, 乳原 善文
    22歳男性。16歳時に持続タンパク尿を認め、腎生検にてfocal segmental glomerulosclerosis(FSGS)と診断され、Prednisolone(PSL)が投与された。今回、腎機能が悪化し、CyA、PSL、MZRで強化されるも効果が乏しく、原因精査の目的で当科へ紹介となった。入院時に高度の感音性難聴が判明し、家族歴より遺伝性腎症の可能性を考え、遺伝子解析および腎生検を実施した。その結果、ミトコンドリア腎症と診断された。以後、血液透析が行われたが、血液透析後に意識消失発作を生じ、腹膜透析に移行するも十分な除水が得られず、母親をドナーとして腎移植を行った。腎移植後は経過良好で、5年経過現在、安定した腎機能が得られている。
    (有)科学評論社, May 2022, 腎臓内科, 15(5) (5), 530 - 535, Japanese

  • 重度小児IgA腎症に対するプレドニゾロン、ミゾリビン、リシノプリルを用いた多剤併用療法の有効性
    島 友子, 向山 弘展, 田中 侑, 貝藤 裕史, 田中 亮二郎, 野津 寛大, 飯島 一誠, 吉川 徳茂, 中西 浩一
    (一社)日本腎臓学会, May 2022, 日本腎臓学会誌, 64(3) (3), 269 - 269, Japanese

  • Akiko Hayakawa-Iwamoto, Daisuke Aotani, Yuki Shimizu, Shota Kakoi, Chie Hasegawa, Shunsuke Itoh, Asami Fujii, Katsushi Takeda, Takashi Yagi, Hiroyuki Koyama, Kenro Imaeda, Kandai Nozu, China Nagano, Hiromi Kataoka, Tomohiro Tanaka
    A 34-year-old man visited our Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, because of dry mouth and weight loss. His plasma glucose level was 32.8 mmol/L and serum levels of ketone bodies were increased, but with metabolic alkalemia. He was also suffering from renal tubular hypomagnesemia and hypokalemia. Abdominal computed tomography showed bilateral renal cysts. These findings were suggestive of maturity-onset diabetes of the young type 5. Genetic testing showed heterozygous hepatocyte nuclear factor 1 beta gene deletion. In the present case, it seemed reasonable to view hepatocyte nuclear factor 1 beta gene deletion as the common cause of maturity-onset diabetes of the young type 5-associated diabetic ketoacidosis and tubular malfunction-induced hypokalemic alkalosis. This case exemplifies the importance of hepatocyte nuclear factor 1 beta gene abnormality as a potential cause of diabetic ketoacidosis with alkalemia.
    May 2022, Journal of diabetes investigation, 13(5) (5), 923 - 926, English, Domestic magazine

  • Yoshitaka Watanabe, Shuichiro Fujinaga, Koji Sakuraya, Hirokazu Ikeda, Kandai Nozu
    BACKGROUND: Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far. METHODS: We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS. RESULTS: At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001). CONCLUSIONS: UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant.
    May 2022, Clinical and experimental nephrology, 26(5) (5), 453 - 459, English, Domestic magazine
    Scientific journal

  • 梅田 千里, 平野 大志, 坂口 晴英, 齋藤 彩, 武政 洋一, 三輪 沙織, 伊藤 亮, 和田 靖之, 長野 智那, 野津 寛大, 大石 公彦
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 168 - 168, Japanese

  • 飯島 一誠, 堀之内 智子, 賈 暁媛, 野津 寛大, 徳永 勝士
    (株)東京医学社, Apr. 2022, 腎と透析, 92(4) (4), 690 - 697, Japanese

  • IV型コラーゲンの三量体構造におけるプロリンの働き
    青砥 悠哉, 高岡 裕, 堀之内 智子, 北角 英晶, 増田 知佳, 近藤 淳, 永井 貞之, 榊原 菜々, 飯島 一誠, 野津 寛大
    発達腎研究会, Apr. 2022, 発達腎研究会誌, 29(1) (1), 19 - 20, Japanese

  • 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 65 - 65, Japanese

  • 青砥 悠哉, 山村 智彦, 堀之内 智子, 北角 英晶, 増田 知佳, 近藤 淳, 永井 貞之, 岡田 絵里, 榊原 菜々, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 109 - 109, Japanese

  • 辻 一七子, 榊原 菜々, 黒崎 雅典, 近藤 淳, 永井 貞之, 青砥 悠哉, 堀之内 智子, 森貞 直哉, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 110 - 110, Japanese

  • 永井 貞之, 堀之内 智子, 増田 知佳, 北角 英晶, 近藤 淳, 青砥 悠哉, 榊原 菜々, 忍頂寺 毅史, 藤村 順也, 石森 真吾, 神吉 直宙, 貝藤 裕史, 島 友子, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 118 - 118, Japanese

  • 北角 英晶, 堀之内 智子, 増田 知佳, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 忍頂寺 毅史, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 154 - 154, Japanese

  • 青砥 悠哉, 森貞 直哉, 坂本 信一, 北角 英晶, 増田 知佳, 永井 貞之, 近藤 淳, 榊原 菜々, 堀之内 智子, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 184 - 184, Japanese

  • 近藤 淳, 長野 智那, 北角 英晶, 増田 知佳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 佐々木 聡, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2022, 日本小児腎臓病学会雑誌, 35(1Suppl.) (1Suppl.), 105 - 105, Japanese

  • Eri Okada, Naoya Morisada, Tomoko Horinouchi, Hideki Fujii, Takayuki Tsuji, Masayoshi Miura, Hideyuki Katori, Masashi Kitagawa, Kunio Morozumi, Takanobu Toriyama, Yuki Nakamura, Ryuta Nishikomori, Sadayuki Nagai, Atsushi Kondo, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Shingo Ishimori, Joichi Usui, Kunihiro Yamagata, Kazumoto Iijima, Toshiyuki Imasawa, Kandai Nozu
    Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD)-MUC1 is predominantly caused by frameshift mutations owing to a single-base insertion into the variable number tandem repeat (VNTR) region in MUC1. Because of the complexity of the variant hotspot, identification using short-read sequencers (SRSs) is challenging. Although recent studies have revealed the usefulness of long-read sequencers (LRSs), the prevalence of MUC1 variants in patients with clinically suspected ADTKD remains unknown. We aimed to clarify this prevalence and the genetic characteristics and clinical manifestations of ADTKD-MUC1 in a Japanese population using an SRS and an LRS. Methods: From January 2015 to December 2019, genetic analysis was performed using an SRS in 48 patients with clinically suspected ADTKD. Additional analyses were conducted using an LRS in patients with negative SRS results. Results: Short-read sequencing results revealed MUC1 variants in 1 patient harboring a cytosine insertion in the second repeat unit of the VNTR region; however, deeper VNTR regions could not be read by the SRS. Therefore, we conducted long-read sequencing analysis of 39 cases and detected MUC1 VNTR variants in 8 patients (in total, 9 patients from unrelated families). With the inclusion of family-affected patients (n = 31), the median age at the development of end-stage kidney disease (ESKD) was 45 years (95% CI: 40-40 years). Conclusion: In Japan, the detection rate of MUC1 variants in patients with clinically suspected ADTKD was 18.8%. More than 20% of patients with negative SRS results had MUC1 variants detected by an LRS.
    Apr. 2022, Kidney international reports, 7(4) (4), 857 - 866, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Rini Rossanti, Tomoko Horinouchi, Tomohiko Yamamura, China Nagano, Nana Sakakibara, Shinya Ishiko, Yuya Aoto, Atsushi Kondo, Sadayuki Nagai, Eri Okada, Shingo Ishimori, Hiroaki Nagase, Satoshi Matsui, Keiichi Tamagaki, Yoshifumi Ubara, Masahiko Nagahama, Yuko Shima, Koichi Nakanishi, Takeshi Ninchoji, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    Background: Alport syndrome is an inherited disorder characterized by progressive renal disease, variable sensorineural hearing loss, and ocular abnormalities. Although many pathogenic variants in COL4A3 and COL4A4 have been identified in patients with autosomal Alport syndrome, synonymous mutations in these genes have rarely been identified. Methods: We conducted in silico splicing analysis using Human Splicing Finder (HSF) and Alamut to predict splicing domain strength and disruption of the sites. Furthermore, we performed in vitro splicing assays using minigene constructs and mRNA analysis of patient samples to determine the pathogenicity of four synonymous variants detected in four patients with suspected autosomal dominant Alport syndrome (COL4A3 [c.693G>A (p.Val231=)] and COL4A4 [c.1353C>T (p.Gly451=), c.735G>A (p.Pro245=), and c.870G>A (p.Lys290=)]). Results: Both in vivo and in vitro splicing assays showed exon skipping in two out of the four synonymous variants identified (c.735G>A and c.870G>A in COL4A4). Prediction analysis of wild-type and mutated COL4A4 sequences using HSF and Alamut suggested these two variants may lead to the loss of binding sites for several splicing factors, e.g., in acceptor sites and exonic splicing enhancers. The other two variants did not induce aberrant splicing. Conclusions: This study highlights the pitfalls of classifying the functional consequences of variants by a simple approach. Certain synonymous variants, although they do not alter the amino acid sequence of the encoded protein, can dramatically affect pre-mRNA splicing, as shown in two of our patients. Our findings indicate that transcript analysis should be carried out to evaluate synonymous variants detected in patients with autosomal dominant Alport syndrome.
    Mar. 2022, Kidney360, 3(3) (3), 497 - 505, English, International magazine
    Scientific journal

  • Hiroshi Kurosawa, Yuko Shiima, Chisato Miyakoshi, Mari Nezu, Maki Someya, Minae Yoshida, Hiroaki Nagase, Kandai Nozu, Yoshiyuki Kosaka, Kazumoto Iijima
    Vital signs are important for patient assessment, but little is known about interpreting those of children in prehospital settings. We conducted an observational study to investigate the association between prehospital vital signs of children and their clinical outcomes in hospitals. We plotted the data of patients with critical outcomes on published reference ranges, such as those of healthy children to evaluate the clinical relevance. Of the 18,493 children screened, 4477 transported to tertiary hospitals were included in the analysis. The outcomes 12 h after being transported to a tertiary hospital were as follows: deceased, 41; hospitalization with critical deterioration events, 65; hospitalization without critical deterioration events, 1086; returned home, 3090; and unknown, 195. The reference ranges of the heart rates (sensitivity: 57.7%, specificity: 67.5%) and respiratory rates (sensitivity: 54.5%, specificity: 67.7%) of healthy children worked best to detect the critical outcomes. Therefore, the reference ranges of healthy children were concluded to be suitable in prehospital settings; however, excessive reliance on vital signs carried potential risks due to their limited sensitivities and specificities. Future studies are warranted to investigate indicators with higher sensitivities and specificities.
    Mar. 2022, Scientific reports, 12(1) (1), 5199 - 5199, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Behavioral Therapy for Children with Avoidant/Restrictive Food Intake Disorder Dependent on Tube or Oral Enteral Nutrient Formula: A Feasibility Study.
    Kazumi Tomioka, Masahiro Nishiyama, Shoichi Tokumoto, Hiroshi Yamaguchi, Kandai Nozu, Hiroaki Nagase
    In children with eating disorders, nutritional status and growth may depend on enteral nutrient formula. Ultimately, its goal is to introduce or reintroduce oral feeding. Japanese research on the treatment of tube or oral formula-dependent children is scarce. This study determined the feasibility of behavioral therapy for children with avoidant/restrictive food intake disorder and dependency on the tube or oral enteral nutrient formula in Japan. Medical records of children diagnosed with this disorder, dependent on the tube or oral enteral nutrient formula and who had received behavioral therapy intervention to withdraw from the formula were retrospectively investigated. We collected their characteristics at first visit and the caloric percentage from oral food intake six months after starting the treatment. In total, four patients (age range: 2-5 years) participated in this study. The feeding routes employed before the intervention were a nasogastric tube for one patient, a gastrostomy bottom for the other patient, and oral formula for the remaining patients (i.e., two children). At the sixth month of the behavioral treatment, none of the patients needed the formula, and the caloric percentage of required nutrition from oral food intake was 100%. Our data demonstrate that this behavioral therapy is feasible for children with avoidant/restrictive food intake disorder dependent on the tube or oral formula in Japan.
    Mar. 2022, The Kobe journal of medical sciences, 67(4) (4), E155-E160, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yasuhiro Oda, Naoki Sawa, Kandai Nozu, Yoshifumi Ubara
    A woman in her 50s with a three-decade history of biopsy-proven focal segmental glomerulosclerosis and a family history of end-stage kidney disease presented with worsening proteinuria and declining kidney function after three decades of immunosuppressive therapy. While a repeat kidney biopsy did not reveal findings diagnostic of Alport syndrome, genetic testing demonstrated a heterozygous mutation in COL4A5, which confirmed the diagnosis of X-linked Alport syndrome. The heterozygous in-frame deletion mutation may explain her intact hearing and relatively mild symptoms. Genetic testing enables diagnosis of Alport syndrome of various phenotypes, some of which cannot be diagnosed conventionally with clinical course and kidney biopsy. Genetic disorders including collagen IV nephropathy should be considered as a differential diagnosis in patients with focal segmental glomerulosclerosis, especially when a patient has early-onset proteinuria, a family history of kidney disease, syndromic features or proteinuria refractory to glucocorticoid treatment.
    Mar. 2022, BMJ case reports, 15(3) (3), English, International magazine
    Scientific journal

  • Mao Shimizu, Hideki Fujii, Keiji Kono, Kentaro Watanabe, Shunsuke Goto, Kandai Nozu, Kimitoshi Nakamura, Shinichi Nishi
    Fabry disease (FD) manifests decreased α-galactosidase A (α-Gal A) activity and multiorgan damage. There are some undiagnosed cases of the condition among patients on dialysis. The prevalence of FD may also vary with the region. Among 227 male patients undergoing maintenance hemodialysis in Awaji Island, a remote island in Japan, 201 (88.5%) were included in this study. Patients with α-Gal A activity <5.0 pmol/h/disk proceeded to secondary screening. Patients with positive secondary screening underwent further genetic analysis. The number of patients with a family history of cardiac, cerebrovascular, and kidney diseases was 31 (15.4%), 23 (11.4%), and 31 (15.4%) patients, respectively. Although three patients (1.5%) had low α-Gal A activity, none of them was positive in the secondary screening. We could not identify any male hemodialysis patient with FD in Awaji Island, even though some patients had a family history of kidney and cardiovascular diseases.
    Mar. 2022, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Shoichi Tokumoto, Masahiro Nishiyama, Hiroshi Yamaguchi, Kazumi Tomioka, Yusuke Ishida, Daisaku Toyoshima, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima, Hiroaki Nagase
    BACKGROUND: Febrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence. METHODS: This was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002-December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007-February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013-April 2016), BCT was indicated for FCSE resistant to fPHT or PB. RESULTS: The rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40). CONCLUSIONS: While the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.
    Mar. 2022, BMC neurology, 22(1) (1), 77 - 77, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 小児科医の意識調査 大事にする価値観は?兵庫県で次に取り組むべき課題は?
    西山 将広, 山本 暢之, 堀之内 智子, 藤岡 一路, 永瀬 裕朗, 野津 寛大
    (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 557 - 557, Japanese

  • 洪本 加奈, 森貞 直哉, 野津 寛大, 飯島 一誠
    3ヵ月男児。特徴的顔貌、発達の遅れ、両側白内障などの精査のため網羅的遺伝子解析を施行した。その結果、診断はアレイCGHによって検出されたKleefstra症候群であったが、エクソーム解析の二次的所見として副腎白質ジストロフィーの原因遺伝子であるABCD1の病的意義不明バリアントを同定した。ABCD1はACMGの勧告で開示が推奨される遺伝子リストには含まれておらず、開示対象とするか苦慮した。本疾患には発症後早期の造血幹細胞移植が有効であり、本バリアントを開示して臨床的評価を行うことは健康管理に有益であると考え、開示した。網羅的遺伝子解析の時代において本例のように開示対象とするか苦慮する例が今後も増加すると予想される。見つかったバリアントの種類や家族の状況だけでなく、様々な要素を考慮し症例ごとに詳細な検討を行うことが重要である。(著者抄録)
    (一社)日本遺伝カウンセリング学会, Mar. 2022, 日本遺伝カウンセリング学会誌, 42(4) (4), 449 - 455, Japanese

  • 兵庫県における治療可能となった難病に対する拡大新生児マススクリーニングの取り組み
    粟野 宏之, 坊 亮輔, 山本 暢之, 李 知子, 上田 雅章, 野津 寛大, 竹島 泰弘, 飯島 一誠
    (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 547 - 547, Japanese

  • 肉眼的血尿をきたした膜性増殖性糸球体腎炎(MPGN)(C3腎症)の1例
    邱 智前, 忍頂寺 毅史, 永井 貞之, 近藤 淳, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 山村 智彦, 堀之内 智子, 平嶋 良章, 貫名 貞之, 吉川 徳茂, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 545 - 546, Japanese

  • 5歳児検尿を契機に発見されたSchimke症候群の1例
    川村 達也, 藤井 順子, 吉本 啓修, 大西 徳子, 権東 雅宏, 梁川 裕司, 横山 直樹, 山本 暢之, 野津 寛大, 吉川 徳茂
    (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 547 - 547, Japanese

  • 尿細管間質性腎炎55例の免疫組織化学染色を用いたIgG subclass検討
    兵頭 俊紀, 原 重雄, 後藤 俊介, 藤井 秀毅, 西 愼一, 野津 寛大, 吉川 徳茂, 吉本 明弘, 伊藤 智雄
    (一社)日本病理学会, Mar. 2022, 日本病理学会会誌, 111(1) (1), 338 - 338, Japanese

  • 生殖細胞系列の網羅的遺伝子解析によって副腎白質ジストロフィーの原因遺伝子であるABCD1のバリアントが二次的に見つかったKleefstra症候群の1例 開示の判断に関与する要素に対する考察
    洪本 加奈, 森貞 直哉, 野津 寛大, 飯島 一誠
    3ヵ月男児。特徴的顔貌、発達の遅れ、両側白内障などの精査のため網羅的遺伝子解析を施行した。その結果、診断はアレイCGHによって検出されたKleefstra症候群であったが、エクソーム解析の二次的所見として副腎白質ジストロフィーの原因遺伝子であるABCD1の病的意義不明バリアントを同定した。ABCD1はACMGの勧告で開示が推奨される遺伝子リストには含まれておらず、開示対象とするか苦慮した。本疾患には発症後早期の造血幹細胞移植が有効であり、本バリアントを開示して臨床的評価を行うことは健康管理に有益であると考え、開示した。網羅的遺伝子解析の時代において本例のように開示対象とするか苦慮する例が今後も増加すると予想される。見つかったバリアントの種類や家族の状況だけでなく、様々な要素を考慮し症例ごとに詳細な検討を行うことが重要である。(著者抄録)
    (一社)日本遺伝カウンセリング学会, Mar. 2022, 日本遺伝カウンセリング学会誌, 42(4) (4), 449 - 455, Japanese

  • Kojima-Ishii Kanako, Nana Sakakibara, Kei Murayama, Koji Nagatani, Satoshi Murata, Akira Otake, Yasutoshi Koga, Hisato Suzuki, Tomoko Uehara, Kenjiro Kosaki, Koh-Ichiro Yoshiura, Hiroyuki Mishima, Yuko Ichimiya, Yuichi Mushimoto, Tomoko Horinouchi, China Nagano, Tomohiko Yamamura, Kazumoto Iijima, Kandai Nozu
    Fanconi syndrome is a functional disorder of the proximal tubule, characterized by pan-aminoaciduria, glucosuria, hypophosphatemia, and metabolic acidosis. With the advancements in gene analysis technologies, several causative genes are identified for Fanconi syndrome. Several mitochondrial diseases cause Fanconi syndrome and various systemic symptoms; however, it is rare that the main clinical symptoms in such disorders are Fanconi syndrome without systematic active diseases like encephalomyopathy or cardiomyopathy. In this study, we analyzed two families exhibiting Fanconi syndrome, developmental disability and mildly elevated liver enzyme levels. Whole-exome sequencing (WES) detected compound heterozygous known and novel BCS1L mutations, which affect the assembly of mitochondrial respiratory chain complex III, in both cases. The pathogenicity of these mutations has been established in several mitochondria-related functional analyses in this study. Mitochondrial diseases with isolated renal symptoms are uncommon; however, this study indicates that mitochondrial respiratory chain complex III deficiency due to BCS1L mutations cause Fanconi syndrome with developmental disability as the primary indications.
    Mar. 2022, Journal of human genetics, 67(3) (3), 143 - 148, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroshi Yamaguchi, Masahiro Nishiyama, Kazumi Tomioka, Hiroto Hongo, Shoichi Tokumoto, Yusuke Ishida, Daisaku Toyoshima, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Hiroaki Nagase
    OBJECTIVE: Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset. METHODS: We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years. RESULTS: In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL). CONCLUSIONS: This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.
    Mar. 2022, Brain & development, 44(3) (3), 210 - 220, English, International magazine
    Scientific journal

  • Toshiyuki Imasawa, Daishi Hirano, Kandai Nozu, Hiroshi Kitamura, Motoshi Hattori, Hitoshi Sugiyama, Hiroshi Sato, Kei Murayama
    Introduction: The clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown. We retrospectively analyzed a cohort of patients with proteinuria, decreased glomerular filtration rate, or Fanconi syndrome who had a genetic mutation confirmed as the cause of MD, defined as mitochondrial nephropathy. Methods: This nationwide survey included 757 nephrology sections throughout Japan, and consequently, data on 81 cases of mitochondrial nephropathy were collected. Results: The most common renal manifestation observed during the disease course was proteinuria. Hearing loss was the most common comorbidity; a renal-limited phenotype was observed only in mitochondrial DNA (mtDNA) point mutation and COQ8B mutation cases. We found a median time delay of 6.0 years from onset of renal manifestations to diagnosis. Focal segmental glomerular sclerosis (FSGS) was the most common pathologic diagnosis. We then focused on 63 cases with the m.3243A>G mutation. The rate of cases with diabetes was significantly higher among adult-onset cases than among childhood-onset cases. Pathologic diagnoses were more variable in adult-onset cases, including diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathy, and minor glomerular abnormalities. During the median observation period of 11.0 years from the first onset of renal manifestations in patients with m.3243A>G, renal replacement therapy (RRT) was initiated in 50.8% of patients. Death occurred in 25.4% of the patients during the median observation period of 12.0 years. The median estimated glomerular filtration rate (eGFR) decline was 5.4 ml/min per 1.73 m2/yr in the cases, especially 8.3 ml/min per 1.73 m2/yr in FSGS cases, with m.3243A>G. Conclusion: Here, we described the clinicopathologic features and prognosis of mitochondrial nephropathy using large-scale data.
    Mar. 2022, Kidney international reports, 7(3) (3), 580 - 590, English, International magazine
    Scientific journal

  • Nana Sakakibara, Kandai Nozu, Tomohiko Yamamura, Tomoko Horinouchi, China Nagano, Ming Juan Ye, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Riku Hamada, Nobuhiko Okamoto, Yuko Shima, Koichi Nakanishi, Masafumi Matsuo, Kazumoto Iijima, Naoya Morisada
    Nephronophthisis is an autosomal-recessive kidney disease that is caused by abnormalities in primary cilia. Nephronophthisis-related ciliopathies (NPHP-RCs) are a common cause of end-stage kidney disease (ESKD) in children and adolescents. NPHP-RCs are often accompanied by extrarenal manifestations, including intellectual disability, retinitis pigmentosa, or polydactyly. Although more than 100 causative genes have been identified, its diagnosis is difficult because the clinical features of each mutation often overlap. From September 2010 to August 2021, we performed genetic analysis, including next-generation sequencing (NGS), in 574 probands with kidney dysfunction and retrospectively studied cases genetically diagnosed with NPHP-RCs. RESULTS: We detected mutations related to NPHP-RCs in 93 patients from 83 families. Members of 60 families were diagnosed using NGS, and the mutations and the corresponding number of families are as follows: NPHP1 (24), NPHP3 (10), OFD1 (7), WDR35 (5), SDCCAG8 (4), BBS10 (3), TMEM67 (3), WDR19 (3), BBS1 (2), BBS2 (2), IFT122 (2), IFT140 (2), IQCB1 (2), MKKS (2), SCLT1 (2), TTC21B (2), ALMS1 (1), ANKS6 (1), BBS4 (1), BBS12 (1), CC2D2A (1), DYNC2H1 (1), IFT172 (1), and MAPKBP1 (1). A total of 39 cases (41.9%) progressed to ESKD at the time of genetic analysis, whereas 58 cases (62.3%) showed extrarenal manifestations, the most common being developmental delay, intellectual disability, and autism spectrum disorder in 44 patients. Comprehensive genetic analysis using NGS is useful for diagnosing patients with NPHP-RCs.
    Feb. 2022, Journal of human genetics, 67(7) (7), 427 - 440, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 長期の塩酸イソプロテレノール持続静注により管理した先天性洞不全症候群を合併した超早産児の一例
    京野 由紀, 垂井 智前, 城戸 拓海, 仲宗根 瑠花, 菅 秀太郎, 阿部 真也, 芦名 満理子, 藤岡 一路, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 251 - 251, Japanese

  • 幼児期の生活習慣と小学1年生の学力との関連 3歳時点での就寝時刻が遅いと学力が低下する
    西山 将広, 徳元 翔一, 山口 宏, 冨岡 和美, 野津 寛大, 永瀬 裕朗
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 369 - 369, Japanese

  • Alport症候群に対するアンチセンス核酸およびスプライシング調節蛋白による治療法の開発
    堀之内 智子, 山村 智彦, Rossanti Rini, 永井 貞之, 近藤 淳, 青砥 悠哉, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 230 - 230, Japanese

  • OCRL異常におけるgenotype-phenotype correlationに関する検討
    榊原 菜々, 北角 英晶, 増田 知佳, 近藤 淳, 永井 貞之, 青砥 悠哉, 堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 253 - 253, Japanese

  • 中等度紫斑病性腎炎へのレニン・アンジオテンシン系阻害薬治療に関する検討
    永井 貞之, 堀之内 智子, 忍頂寺 毅史, 近藤 淳, 青砥 悠哉, 榊原 菜々, 石森 真吾, 藤村 順也, 神吉 直宙, 貝藤 裕史, 田中 亮二郎, 島 友子, 飯島 一誠, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 255 - 255, Japanese

  • 遺伝子解析が早期診断の一助となった中枢性尿崩症の1家系
    北角 英晶, 堀之内 智子, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 375 - 375, Japanese

  • 一次急病施設における異物・毒物誤飲診療の現状と課題
    忍頂寺 毅史, 近藤 淳, 石河 慎也, 運崎 愛, 山口 宏, 林 卓郎, 田中 亮二郎, 永瀬 裕朗, 石田 明人, 野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 308 - 308, Japanese

  • ミトコンドリアDNA修復遺伝子であるDNA Ligase IIIは新規ミトコンドリア病の原因遺伝子である(Mutations in LIG3 cause mitochondrial neurogastrointestinal encephalomyopathy by mtDNA depletion)
    池田 真理子, 親里 嘉展, 内野 俊平, 三牧 正和, 野津 寛大, 森岡 一朗, 大竹 明, 小崎 健次郎, 飯島 一誠
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 238 - 238, English

  • Hiromichi Yoshimoto, Takeshi Ninchoji, Sadayuki Nagai, Tomoko Horinouchi, Kandai Nozu
    Feb. 2022, CEN case reports, 11(1) (1), 159 - 160, English, Domestic magazine

  • Shinya Ishiko, Naoya Morisada, Atsushi Kondo, Sadayuki Nagai, Yuya Aoto, Eri Okada, Rini Rossanti, Nana Sakakibara, China Nagano, Tomoko Horinouchi, Tomohiko Yamamura, Takeshi Ninchoji, Hiroshi Kaito, Riku Hamada, Yuko Shima, Koichi Nakanishi, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 gene. The clinical spectrum is often more variable than previously considered. We aimed to analyze the clinical features of genetically diagnosed ARPKD in the Japanese population. METHODS: We conducted a genetic analysis of patients with clinically diagnosed or suspected ARPKD in Japan. Moreover, we performed a minigene assay to elucidate the mechanisms that could affect phenotypes. RESULTS: PKHD1 pathogenic variants were identified in 32 patients (0-46 years). Approximately one-third of the patients showed prenatal anomalies, and five patients died within one year after birth. Other manifestations were detected as follows: chronic kidney disease stages 1-2 in 15/26 (57.7%), Caroli disease in 9/32 (28.1%), hepatic fibrosis in 7/32 (21.9%), systemic hypertension in 13/27 (48.1%), and congenital hypothyroidism in 3 patients. There have been reported that truncating mutations in both alleles led to severe phenotypes with perinatal demise. However, one patient without a missense mutation survived the neonatal period. In the minigene assay, c.2713C > T (p.Gln905Ter) and c.6808 + 1G > A expressed a transcript that skipped exon 25 (123 bp) and exon 41 (126 bp), resulting in an in-frame mutation, which might have contributed to the milder phenotype. Missense mutations in cases of neonatal demise did not show splicing abnormalities. CONCLUSION: Clinical manifestations ranged from cases of neonatal demise to those diagnosed in adulthood. The minigene assay results indicate the importance of functional analysis, and call into question the fundamental belief that at least one non-truncating mutation is necessary for perinatal survival.
    Feb. 2022, Clinical and experimental nephrology, 26(2) (2), 140 - 153, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Miki Murakoshi, Koichi Kamei, Masao Ogura, Mai Sato, Taishi Nada, Ryutaro Suzuki, Chikako Kamae, Kentaro Nishi, Toru Kanamori, China Nagano, Kandai Nozu, Koichi Nakanishi, Kazumoto Iijima
    BACKGROUND: The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. METHODS: Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. RESULTS: Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59-208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. CONCLUSIONS: Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.
    Feb. 2022, Clinical and experimental nephrology, 26(2) (2), 162 - 169, English, Domestic magazine
    Scientific journal

  • Megumi Nagai-Sangawa, Atsushi Fukunaga, Chihiro Takeuchi, Satoshi Nishiyama, Tatsuya Horikawa, China Nagano, Kandai Nozu, Hideki Fujii, Chikako Nishigori
    Fabry disease (FD), which is a lysosomal storage disease resulting from a deficiency of α-galactosidase A, leads to the accumulation of globotriaosylceramide in various tissues and multiorgan impairment. Early diagnosis is important to improve long-term prognosis. Early clinical manifestations of FD include neuropathic pain, vascular skin lesions, and sweating abnormalities. Hypohidorosis is one of the clinical findings in the early stage of FD. However, there have been no studies on prospective screening of FD in patients with definitive diagnosis of hypohidrosis. We examined α-galactosidase A activity in white blood cells in 17 (one female and 16 male) patients with generalized hypohidorosis. Among 17 patients, one male patient (approximately 5.8%) had significantly reduced α-galactosidase A activity. He presented with a history of hypohidrosis with heat intolerance and neuropathic tingling pain in a warm environment from 6 years ago. He had a few angiokeratoma on the trunk and extremities. Ultrastructural examination of skin biopsy from the angiokeratoma revealed lamellar inclusions in endothelial cells. Kidney biopsy revealed swollen podocytes and Gb3 deposition in the glomerulus, and urinalysis revealed mulberry bodies. He was finally diagnosed with FD and started on enzyme replacement therapy with agalsidase alpha in the early stage. In addition, his family screening led to find the patients of four additional FD. Screening for FD in patients with hypohidrosis may lead to efficient early detection of FD.
    Feb. 2022, The Journal of dermatology, 49(2) (2), 308 - 312, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kazumoto Iijima, Mayumi Sako, Mari Oba, Seiji Tanaka, Riku Hamada, Tomoyuki Sakai, Yoko Ohwada, Takeshi Ninchoji, Tomohiko Yamamura, Hiroyuki Machida, Yuko Shima, Ryojiro Tanaka, Hiroshi Kaito, Yoshinori Araki, Tamaki Morohashi, Naonori Kumagai, Yoshimitsu Gotoh, Yohei Ikezumi, Takuo Kubota, Koichi Kamei, Naoya Fujita, Yasufumi Ohtsuka, Takayuki Okamoto, Takeshi Yamada, Eriko Tanaka, Masaki Shimizu, Tomoko Horinouchi, Akihide Konishi, Takashi Omori, Koichi Nakanishi, Kenji Ishikura, Shuichi Ito, Hidefumi Nakamura, Kandai Nozu
    BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
    Feb. 2022, Journal of the American Society of Nephrology : JASN, 33(2) (2), 401 - 419, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nana Sakakibara, Takeshi Ijuin, Tomoko Horinouchi, Tomohiko Yamamura, China Nagano, Eri Okada, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Takeshi Ninchoji, Hiroyuki Awano, Hiroaki Nagase, Shogo Minamikawa, Ryojiro Tanaka, Takeshi Matsuyama, Koji Nagatani, Koichi Kamei, Kumiko Jinnouchi, Yasufumi Ohtsuka, Masafumi Oka, Yoshinori Araki, Toju Tanaka, Mari S Harada, Toru Igarashi, Hikaru Kitahara, Naoya Morisada, Shun-Ichi Nakamura, Taro Okada, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1-7 lead to Dent disease-2, whereas those in exons 8-24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms. METHODS: Messenger RNA samples extracted from cultured urine-derived cells from a healthy control and a Dent disease-2 patient were examined to detect the 5' end of the OCRL isoform. For protein expression and functional analysis, vectors containing the full-length OCRL transcripts, the isoform transcripts and transcripts with truncating mutations detected in Lowe syndrome and Dent disease-2 patients were transfected into HeLa cells. RESULTS: We successfully cloned the novel isoform transcripts from OCRL exons 6-24, including the translation-initiation codons present in exon 8. In vitro protein-expression analysis detected proteins of two different sizes (105 and 80 kDa) translated from full-length OCRL, whereas only one protein (80 kDa) was found from the isoform and Dent disease-2 variants. No protein expression was observed for the Lowe syndrome variants. The isoform enzyme activity was equivalent to that of full-length OCRL; the Dent disease-2 variants retained >50% enzyme activity, whereas the Lowe syndrome variants retained <20% activity. CONCLUSIONS: We elucidated the molecular mechanism underlying the two different phenotypes in OCRL-related diseases; the functional OCRL isoform translated starting at exon 8 was associated with this mechanism.
    Jan. 2022, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 37(2) (2), 262 - 270, English, International magazine
    Scientific journal

  • Sadayuki Nagai, Tomoko Horinouchi, Takeshi Ninchoji, Atsushi Kondo, Yuya Aoto, Shinya Ishiko, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Hiroshi Kaito, Ryojiro Tanaka, Yuko Shima, Junya Fujimura, Naohiro Kamiyoshi, Shingo Ishimori, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Cases of Henoch-Schönlein purpura nephritis (HSPN) with moderate severity were demonstrated to achieve good prognosis after treatment with renin-angiotensin system (RAS) inhibitors. However, some patients required additional treatment for recurrence after remission. This study aimed to clarify the effect of RAS inhibitors in HSPN cases with moderate severity, including the proportion of cases with recurrence and their response to additional treatment. METHODS: Among 126 patients diagnosed with HSPN between 1996 and 2019, 71 patients with clinicopathologically diagnosed HSPN of moderate severity, defined as ISKDC grade II-IIIa and serum albumin ≥ 2.5 g/dL, were investigated. RESULTS: Proteinuria became negative after RAS inhibitor treatment alone in all 71 cases. However, 16 (22.5%) had recurrence. Eleven recurrent cases achieved negative proteinuria again following additional treatment. At the last follow-up (median 46.5 months; IQR, 23.2-98.2), 5 patients had persistent mild proteinuria; no patients had estimated glomerular filtration rate < 90 mL/min/1.73 m2. The pathological findings in all recurrent cases were ISKDC grade IIIa. The 16 recurrent cases had significantly higher proportions of glomeruli with global/segmental sclerosis (25.0 vs. 0%, P < 0.001) and tubular atrophy/interstitial fibrosis (37.5 vs. 12.7%, P =0.0 24) than 55 cases without recurrence. CONCLUSIONS: Japanese childhood HSPN cases with moderate severity had good outcomes without need for corticosteroids or immunosuppressants, when prescribed RAS inhibitor treatment. Even in recurrent cases, abnormal proteinuria was transient, and prognosis was excellent. A higher resolution version of the Graphical abstract is available as Supplementary information.
    Jan. 2022, Pediatric nephrology (Berlin, Germany), 37(8) (8), 1845 - 1853, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoko Horinouchi, Kandai Nozu, Kazumoto Iijima
    Idiopathic nephrotic syndrome is the most common childhood glomerular disease. Most forms of this syndrome respond to corticosteroids at standard doses and are, therefore, defined as steroid-sensitive nephrotic syndrome (SSNS). Immunological mechanisms and subsequent podocyte disorders play a pivotal role in SSNS and have been studied for years; however, the precise pathogenesis remains unclear. With recent advances in genetic techniques, an exhaustive hypothesis-free approach called a genome-wide association study (GWAS) has been conducted in various populations. GWASs in pediatric SSNS peaked in the human leukocyte antigen class II region in various populations. Additionally, an association of immune-related CALHM6/FAM26F, PARM1, BTNL2, and TNFSF15 genes, as well as NPHS1, which encodes nephrin expressed in podocytes, has been identified as a locus that achieves genome-wide significance in pediatric SSNS. However, the specific mechanism of SSNS development requires elucidation. This review describes an updated view of SSNS pathogenesis from immunological and genetic aspects, including interactions with infections or allergies, production of circulating factors, and an autoantibody hypothesis.
    Jan. 2022, Pediatric nephrology (Berlin, Germany), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Masashi Fujita, Tomomi Aizawa, Koji Tsugawa, Deborah Mattinzoli, Kandai Nozu, Kensuke Joh, Hiroshi Tanaka
    Jan. 2022, Pediatrics international : official journal of the Japan Pediatric Society, 64(1) (1), e15350, English, International magazine
    Scientific journal

  • Hiroshi Yamaguchi, Kandai Nozu, Shinya Ishiko, Hiroaki Nagase, Takeshi Ninchoji, China Nagano, Hiroki Takeda, Ai Unzaki, Kazuto Ishibashi, Ichiro Morioka, Kazumoto Iijima, Akihito Ishida
    INTRODUCTION: Previous studies reported a dramatic decline in the incidence of varicella and varicella-related deaths after implementing universal varicella vaccination (VarV). Although previous studies reported the effectiveness and economic impact of VarV, they were unknown in the emergency department (ED) setting. METHODS: To determine the effectiveness and economic impact of VarV in the ED, Kobe, Japan, we retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED from 2011 to 2019. RESULTS: Of the 265,191 children presenting to our ED, 3,092 patients were clinically diagnosed with varicella. The number of patients with varicella was approximately 500 annually, before introducing the universal two-dose VarV for children aged 1 to <3 years in October 2014, in the Japanese national immunization program, and decreased to approximately 200 in 2019. The number of patients with varicella younger than 1 year (ineligible for the vaccination) also decreased. Regarding the economic impact, the medical cost in our ED reduced after the introduction of VarV was JPY 4.1 million (US$ 40,049) annually. From the central data, approximately 95% of children were vaccinated after October 2014; however, a relatively large percentage of infected unvaccinated children (59.0%) presented to ED in this study. After the implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation). CONCLUSIONS: Our data showed the effectiveness and economic impact of VarV in the ED setting. Additionally, our data suggested that the public vaccination program should include older unvaccinated children and other unvaccinated individuals.
    Jan. 2022, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 28(1) (1), 35 - 40, English, International magazine
    Scientific journal

  • Yuya Aoto, Tomoko Horinouchi, Tomohiko Yamamura, Atsushi Kondo, Sadayuki Nagai, Shinya Ishiko, Eri Okada, Rini Rossanti, Nana Sakakibara, China Nagano, Hiroyuki Awano, Hiroaki Nagase, Yuko Shima, Koichi Nakanishi, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    INTRODUCTION: COL4A5 is a causative gene of X-linked Alport syndrome (XLAS). Male patients with XLAS with nonsense variants have the most severe phenotypes of early onset end-stage kidney disease (ESKD); those with splicing variants have middle phenotypes and those with missense variants have the mildest phenotypes. Therefore, genotyping for male patients with XLAS can be used to predict kidney prognosis. Single-base substitutions at the last nucleotide position in each exon are known to affect splicing patterns and could be splicing variants. Nevertheless, in XLAS, these variants are generally considered to be missense variants, without conducting a transcript analysis, which underestimates some patients as having mild phenotypes. This study aimed to investigate whether single-base substitutions at the last nucleotide position of COL4A5 exons cause aberrant splicing. METHODS: In total, 20 variants were found in the Human Gene Mutation Database (n = 14) and our cohort (n = 6). We performed functional splicing assays using a hybrid minigene analysis and in vivo transcript analyses of patients' samples when available. Then, we investigated genotype-phenotype correlations for patients with splicing variants detected in this study by comparing data from our previous studies. RESULTS: Among the 20 variants, 17 (85%) caused aberrant splicing. Male patients with splicing variants had more severe phenotypes when compared with those with missense variants. Findings from the in vivo analyses for 3 variants were identical to those from the minigene assay. CONCLUSION: Our study revealed that most single-base substitutions at the last nucleotide position of COL4A5 exons result in splicing variants, rather than missense variants, thereby leading to more severe phenotypes.
    Jan. 2022, Kidney international reports, 7(1) (1), 108 - 116, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomohiko Yamamura, Tomoko Horinouchi, Yuya Aoto, Rachel Lennon, Kandai Nozu
    X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 and is characterized by progressive kidney disease, hearing loss, and ocular abnormalities. Recent advances in genetic analysis and further understanding of genotype-phenotype correlations in affected male patients raises the importance of detecting splicing variants in COL4A5. Aberrant splicing of COL4A5 is caused not only by canonical splice site variants but also non-canonical splice site variants such as deep intronic changes or even substitutions in exons. Patients with splicing variants account for ~15% of all cases in XLAS. In addition, it has been shown that there is a significant difference in kidney survival depending on the aberrant splicing patterns of transcripts- in particular in-frame or out-of-frame nucleotide changes in transcripts. Therefore, cDNA analysis of patient mRNA is necessary to determine the impact of splice site variants and to confirm a diagnosis of XLAS and to predict the kidney prognosis. However, it is usually difficult to amplify COL4A5 transcripts extracted from peripheral blood leukocytes. For these cases, in vitro minigene assays or RNA sequence extracted from urine derived cells can confirm aberrant splicing patterns. Moreover, controlling aberrant splicing by nucleic acids or small molecular compounds in genetic diseases are attracting attention as a potential therapeutic strategy. Here, we review the frequency of splicing variants in COL4A5, the latest diagnostic strategies, and the prospects for new therapeutic approaches.
    2022, Frontiers in medicine, 9, 841391 - 841391, English, International magazine
    Scientific journal
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  • Yukimasa Taniguchi, China Nagano, Kiyotoshi Sekiguchi, Atsushi Tashiro, Noriko Sugawara, Haruhide Sakaguchi, Chisato Umeda, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, Tomoko Horinouchi, Tomohiko Yamamura, Atsushi Kondo, Sadayuki Nagai, Hiroaki Nagase, Kazumoto Iijima, Jeffrey H Miner, Kandai Nozu
    Background: Pathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid-resistant nephrotic syndrome (SRNS) patients in children. However, LAMA5 gene biallelic variants have been identified in only seven patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome, and one patient with SRNS with biallelic LAMA5 missense variants. Methods: We conducted comprehensive gene screening of Japanese patients with severe proteinuria. With the use of targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered LAMA5 variants, we conducted in vitro heterotrimer formation assays. Results: Biallelic truncating variants in the LAMA5 gene (NM_005560) were detected in three patients from two families. All patients presented with proteinuria within 6 months of age. Patients 1 and 2 were siblings possessing a nonsense variant (c.9232C>T, p.[Arg3078*]) and a splice site variant (c.1282 + 1G>A) that led to exon 9 skipping and a frameshift. Patient 3 had a remarkable irregular contour of the glomerular basement membrane. She was subsequently found to have a nonsense variant (c.8185C>T, p.[Arg2720*]) and the same splice site variant in patients 1 and 2. By in vitro heterotrimer formation assays, both truncating variants produced smaller laminin α5 proteins that nevertheless formed trimers with laminin β1 and γ1 chains. Patient 4 showed SRNS at the age of 8 years, and carried compound heterozygous missense variants (c.1493C>T, p.[Ala498Val] and c.8399G>A, p.[Arg2800His]). Conclusions: Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathologic characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in patients with congenital/infantile nephrotic syndrome.
    Dec. 2021, Kidney360, 2(12) (12), 1968 - 1978, English, International magazine
    Scientific journal

  • Takumi Kido, Yuki Kyono, Shutaro Suga, Ruka Nakasone, Shinya Abe, Mariko Ashina, Hisayuki Matsumoto, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka
    For symptomatic congenital cytomegalovirus infections (CCMVI), the usefulness of changes in viral load during valganciclovir (VGCV) treatment for the prediction of hearing dysfunction (HD) is unclear. To determine the utility of viral load change in the whole blood or urine for the prediction of HD, we performed a retrospective study to compare viral load changes during VGCV treatment between CCMVI infants with (n = 12) or without (n = 8) HD at six months of corrected age, whose blood and urine viral loads were measured continuously for eight weeks from April 2009 to December 2019. There was no significant difference in the changes in both the blood and urine viral loads after the initiation of VGCV treatment between CCMVI infants between the groups. Moreover, this negative result was maintained in the analysis for each six weeks or six months treatment period. In conclusion, the change in viral load during antiviral therapy is not useful for the prediction of HD at six months of corrected age in symptomatic CCMVI.
    Dec. 2021, Journal of clinical medicine, 10(24) (24), English, International magazine
    Scientific journal
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  • Ruka Nakasone, Mariko Ashina, Takumi Kido, Harunori Miyauchi, Masafumi Saito, Shigeaki Inoue, Masakazu Shinohara, Kandai Nozu, Kazumichi Fujioka
    Neonatal sepsis is characterized by systemic bacterial invasion followed by a massive inflammatory response. At present, no therapeutic strategy has been found that significantly reduces the mortality of neonatal sepsis. We aimed to investigate the protective role of an initial low-dose septic challenge for the prevention of subsequent lethal sepsis in a mouse model. A stock cecal slurry (CS) solution was prepared from adult ceca. The LD83 (1.5 mg CS/g) was used for all animals. An initial challenge of normal saline (NS) or 0.5 mg CS/g (non-lethal dose) was administered at four days of age, then 1.5 mg CS/g was administered intraperitoneally at seven days of age (72 h post-initial challenge), and survival was monitored. Initial exposure to NS (n = 10) resulted in 90% mortality following exposure to the LD83 CS dose in contrast to an initial exposure to CS (n = 16), which significantly decreased mortality to 6% (p < 0.0001), reduced blood bacterial counts, attenuated inflammatory responses, and suppressed lipid mediators. Initial exposure to a non-lethal CS dose prior to exposure to a lethal CS dose significantly reduces sepsis mortality, a protective effect that might be mediated by modulating abnormal systemic inflammatory responses.
    Dec. 2021, Journal of clinical medicine, 10(24) (24), English, International magazine
    Scientific journal
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  • Takehiko Wada, Takuji Ishimoto, Izaya Nakaya, Takehiko Kawaguchi, Tadashi Sofue, Sayaka Shimizu, Noriaki Kurita, Sho Sasaki, Hiroki Nishiwaki, Masahiro Koizumi, Shoji Saito, Nobuhiro Nishibori, Yuji Oe, Mai Yoshida, Yoshitaka Miyaoka, Shin'ichi Akiyama, Yuya Itano, Masaki Okazaki, Takaya Ozeki, Daisuke Ichikawa, Hideyo Oguchi, Satoshi Kohsaka, Shiho Kosaka, Yuki Kataoka, Hideaki Shima, Sayuri Shirai, Kazuhiro Sugiyama, Tomo Suzuki, Daisuke Son, Tomomi Tanaka, Eishu Nango, Kakuya Niihata, Yoko Nishijima, Kandai Nozu, Midori Hasegawa, Rei Miyata, Masahiko Yazawa, Yoshihiro Yamamoto, Ryohei Yamamoto, Yugo Shibagaki, Kengo Furuichi, Hirokazu Okada, Ichiei Narita
    Dec. 2021, Clinical and experimental nephrology, 25(12) (12), 1277 - 1285, English, Domestic magazine
    Scientific journal

  • Hiroshi Yamaguchi, Kandai Nozu, Shinya Ishiko, Atsushi Kondo, Nobuyuki Yamamoto, Akihiro Tamura, Yuya Aoto, Ai Unzaki, Kazuto Ishibashi, Ichiro Morioka, Hiroaki Nagase, Akihito Ishida
    BACKGROUND: An unprovoked seizure is a seizure or a cluster of seizures occurring within 24 h in a patient older than 1 month of age without precipitating factors. Recent studies have reported that extrinsic factors, such as meteorological conditions and air pollutants, may be important in seizure occurrence. Thus, this study aimed to examine the association between the number of visits to the emergency department (ED) by children for nighttime unprovoked seizures and exposure to multi-faceted factors, such as meteorological conditions and air pollution. METHODS: We conducted a clinical observational analysis and reviewed consecutive patients younger than 16 years of age who visited the primary ED center in Kobe City, Japan, during nighttime (7:30 p.m.-7:00 a.m.) between January 1, 2011 and December 31, 2015. We investigated the effects of meteorological factors and air pollutants on the number of patients with unprovoked seizures using multivariate analysis of Poisson regression estimates. RESULTS: In total, 151,119 children visited the ED, out of which 97 patients presented with unprovoked seizures. The mean age of the patients was 4.7 years (range, 1 month to 15.3 years), and 54.6% of them were boys. The total number of patients with unprovoked seizures showed no significant changes with the seasons; however, there were dominant peaks during the fall and fewer visits during the summer. The multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients presenting with unprovoked seizures and precipitation (+1 patient/87 mm; p = 0.03) and methane (+1 patient/0.14 ppm; p = 0.03) levels and a negative relationship between the number of patients presenting with unprovoked seizures and nitrogen dioxide level (-1 patient/0.02 ppm; p = 0.04). CONCLUSIONS: The present study is the first to evaluate the association between the number of children who presented to the ED with nighttime unprovoked seizures and environmental factors after controlling for confounding factors.
    Dec. 2021, Epilepsy & behavior : E&B, 125, 108434 - 108434, English, International magazine
    Scientific journal

  • Jing Wu, Jun Zhang, Li Liu, Bo Zhang, Tomohiko Yamamura, Kandai Nozu, Masafumi Matsuo, Jinghong Zhao
    BACKGROUND: Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants. METHODS: A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants. RESULTS: Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991-14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis. CONCLUSION: A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.
    Nov. 2021, BMC nephrology, 22(1) (1), 380 - 380, English, International magazine
    Scientific journal

  • 堀之内 智子, 山村 智彦, 永井 貞之, 近藤 淳, 青砥 悠哉, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, Nov. 2021, 日本小児腎臓病学会雑誌, 34(2) (2), 177 - 177, Japanese

  • 近藤 淳, 堀之内 智子, 山村 智彦, 永井 貞之, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 野津 寛大, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2021, 日本小児腎臓病学会雑誌, 34(2) (2), 204 - 205, Japanese

  • 稲葉 彩, 出崎 緑, 出来 沙織, 内村 暢, 坂 早苗, 平和 伸仁, 千葉 佐和子, 大谷 方子, 伊藤 秀一, 大坪 裕美, 野津 寛大, 城 謙輔
    (一社)日本小児腎臓病学会, Nov. 2021, 日本小児腎臓病学会雑誌, 34(2) (2), 188 - 189, Japanese

  • 近藤 淳, 堀之内 智子, 山村 智彦, 永井 貞之, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 野津 寛大, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2021, 日本小児腎臓病学会雑誌, 34(2) (2), 204 - 205, Japanese

  • 稲葉 彩, 出崎 緑, 出来 沙織, 内村 暢, 坂 早苗, 平和 伸仁, 千葉 佐和子, 大谷 方子, 伊藤 秀一, 大坪 裕美, 野津 寛大, 城 謙輔
    (一社)日本小児腎臓病学会, Nov. 2021, 日本小児腎臓病学会雑誌, 34(2) (2), 188 - 189, Japanese

  • Kentaro Nishi, Koichi Kamei, Masao Ogura, Mai Sato, Sho Ishiwa, Yoko Shioda, Chikako Kiyotani, Kimikazu Matsumoto, Kandai Nozu, Kenji Ishikura, Shuichi Ito
    Nov. 2021, Pediatric nephrology (Berlin, Germany), 36(11) (11), 3805 - 3806, English, International magazine

  • Hiroshi Yamaguchi, Kandai Nozu, Shinya Ishiko, Atsushi Kondo, Takeshi Ninchoji, China Nagano, Hiroki Takeda, Ai Unzaki, Kazuto Ishibashi, Ichiro Morioka, Hiroaki Nagase, Kazumoto Iijima, Akihito Ishida
    The coronavirus disease (COVID-19) pandemic altered environmental factors. We studied the impact of these changes on asthma exacerbation (AE) by comparing the AE-related environmental factors between COVID-19 (2020) and pre-COVID-19 (2011-2019) eras. Between 2011 and 2020, 278,465 children (<16 years old) visited our emergency department, and 7476 were diagnosed with AE. The number of patients showed spring and fall peaks in 2011-2019. Multivariate analyses showed significant positive relationships of the number of AE patients with the average temperature among all patients and 0-5-year-olds and with sulfur dioxide (SO2) levels in 2011-2019 among 0-5-year-olds. Although the spring peak in the number of patients was not observed in 2020 after declaration of a state of emergency, the fall peak was again observed after the state of emergency was lifted. No changes in average temperature were detected, but SO2 was significantly reduced following declaration of the state of emergency in 2020. Therefore, SO2 reduction might have contributed to the disappearance of the peak of AE. However, a fall peak was observed again in 2020, although SO2 levels continued to be low. These data suggest that person to person interaction seems to be associated with AE, presumably due to unknown viral infections.
    Oct. 2021, International journal of environmental research and public health, 18(21) (21), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Mariko Ashina, Takumi Kido, Yuki Kyono, Asumi Yoshida, Shutaro Suga, Ruka Nakasone, Shinya Abe, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka
    Severe small-for-gestational-age (sSGA) infants exhibit increased mortality and morbidity. Oxidative stress is suggested to be involved in intrauterine growth restriction. This retrospective study aimed to evaluate the oxidative stress level at birth in an sSGA population. Sera of 28 sSGA (sSGA group) and 31 non-sSGA (control group) infants, born at our hospital between March 2017 and March 2020, were evaluated. Oxidative stress (derivative of reactive oxidative metabolites: d-ROM level), biological antioxidant potential (BAP) level, and the ratio of d-ROM/BAP level (oxidative stress index: OSI) were measured. The sSGA group had a significantly lower birth weight (BW), BW z-score, head circumference, and height than the control group (all p < 0.05). No significant difference was noted in the BAP level; sSGA infants exhibited a significantly higher d-ROM level than control infants. sSGA infants showed a significantly increased OSI compared with control infants, and the BW z-score was inversely correlated with d-ROM levels and OSI in sSGA infants (R2 = 0.300; p < 0.01 and R2 = 0.319; p = 0.02, respectively) but not in controls. In conclusion, sSGA infants, including preterm infants, exhibited higher oxidative stress at birth. The severity of fetal growth restriction was significantly correlated with oxidative stress levels at birth in sSGA infants.
    Oct. 2021, International journal of environmental research and public health, 18(20) (20), English, International magazine
    Scientific journal
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  • 症候性先天性サイトメガロウイルス感染症を対象とした抗ウイルス薬治療の医師主導治験の進捗
    森岡 一朗, 伊藤 嘉規, 吉川 哲史, 森内 浩幸, 高橋 尚人, 藤岡 一路, 野津 寛大, 児玉 知之, 筧 康正, 岡 明
    (一社)日本小児感染症学会, Oct. 2021, 日本小児感染症学会総会・学術集会プログラム・抄録集, 53回, 122 - 122, Japanese

  • Satoshi Takemori, Shinji Tanigaki, Kandai Nozu, Hiroshi Yoshihashi, Yutaro Uchiumi, Kyoko Sakaguchi, Kana Tsushima, Aya Kitamura, Chie Kobayashi, Miho Matsuhima, Atsushi Tajima, China Nagano, Yoichi Kobayashi
    Transient antenatal Bartter syndrome due to melanoma-associated antigen D2 gene mutation is a newly reported type of Bartter syndrome. Its characteristics include an X-linked inheritance pattern, early-onset hydramnios, and spontaneous disappearance of symptoms after childbirth. To date, there have been no reports of prenatally diagnosed cases. We herein present the case of a preterm male born to a mother with early-onset hydramnios and a family history of X-linked idiopathic hydramnios. We suspected melanoma-associated antigen D2 gene mutation and performed direct sequencing. As a result, we were able to prenatally establish a diagnosis of transient Bartter syndrome due to a melanoma-associated antigen D2 gene mutation.
    Oct. 2021, European journal of medical genetics, 64(10) (10), 104308 - 104308, English, International magazine
    Scientific journal

  • Yurika Tsuji, Tomohiko Yamamura, China Nagano, Tomoko Horinouchi, Nana Sakakibara, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Eri Okada, Eriko Tanaka, Koji Tsugawa, Takayuki Okamoto, Toshihiro Sawai, Yoshinori Araki, Yuko Shima, Koichi Nakanishi, Hiroaki Nagase, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    INTRODUCTION: Frasier syndrome (FS) is a rare inherited kidney disease caused by intron 9 splicing variants of WT1. For wild-type WT1, 2 active splice donor sites in intron 9 cause a mixture of 2 essential transcripts (with or without lysine-threonine-serine [+/KTS or -KTS]), and imbalance of the +KTS/-KTS ratio results in the development of FS. To date, 6 causative intron 9 variants have been identified; however, detailed transcript analysis has not yet been conducted and the genotype-phenotype correlation also remains to be elucidated. METHODS: We conducted an in vitro minigene splicing assay for 6 reported causative variants and in vivo RNA sequencing to determine the +KTS/-KTS ratio using patients' samples. We also performed a systematic review of reported FS cases with a description of the renal phenotype. RESULTS: The in vitro assay revealed that although all mutant alleles produced -KTS transcripts only, the wild-type allele produced both +KTS and -KTS transcripts at a 1:1 ratio. In vivo RNA sequencing showed that patients' samples with all heterozygous variants produced similar ratios of +KTS to -KTS (1:3.2-1:3.5) and wild-type kidney showed almost a 1:1 ratio (1:0.85). A systematic review of 126 cases clarified that the median age of developing ESKD was 16 years in all FS patients, and there were no statistically significant differences between the genotypes or sex chromosome karyotypes in terms of the renal survival period. CONCLUSION: Our study suggested no differences in splicing pattern or renal survival period among reported intron 9 variants causative of FS.
    Oct. 2021, Kidney international reports, 6(10) (10), 2585 - 2593, English, International magazine
    Scientific journal
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  • Takeshi Ninchoji, Kandai Nozu, Atsushi Kondo, Shinya Ishiko, Ai Unzaki, China Nagano, Hiroshi Yamaguchi, Hiroki Takeda, Takuro Hayashi, Ryojiro Tanaka, Hiroaki Nagase, Kazumoto Iijima, Akihito Ishida
    OBJECTIVES: Accidental foreign body ingestion (FBI) and toxic agent ingestion (TAI) are commonly encountered among children in primary emergency settings. Early detection and appropriate medical intervention are crucial to improve outcomes. Although many reports from tertiary institutions have shown improvements in therapy, data are still lacking from primary emergency facilities. METHODS: We performed a retrospective analysis based on medical records of FBI/TAI over 4 years at the Kobe Children's Primary Emergency Medical Center. We collected patient information, including age, sex, time between FBI/TAI occurrence and centre visit, provision of first aid, symptoms, type of FBI/TAI, examinations, treatments, and outcomes. RESULTS: A total of 580 children were enrolled. The median age was 1.3 years, and patients under 2 years old accounted for 70% of total cases. Cigarettes (17.5%) were the most common ingested foreign body, followed by medicines (15.3%), detergents (8.1%), in TAI, plastics (14.1%), metal (13.4%), batteries (9.0%) in FBI, and others (22.6%). A total of 42 patients were transferred to advanced hospitals; among these, 22 patients were hospitalised but the foreign body was removed in only 3 (0.9%) patients. Transferred patients were significantly older (P<0.05) in FBI and had a higher rate of any of symptoms (P<0.05) in FBI/TAI. CONCLUSIONS: This large-scale retrospective study of accidental FBI/TAI conducted at a primary emergency facility clarified current management, including treatment at a primary facility. Very few cases of FBI/TAI were treated, even when they were transferred to an advanced treatment hospital. Unified protocols should be established, to improve the management of FBI/TAI.
    Sep. 2021, Minerva pediatrics, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 腎臓研究の最前線 GWASを用いた腎疾患感受性遺伝子同定
    飯島 一誠, 堀之内 智子, 野津 寛大
    (一社)日本腎臓学会, Sep. 2021, 日本腎臓学会誌, 63(6-E) (6-E), 658 - 658, Japanese

  • COL4A5遺伝子のエクソン3'末端に位置する一塩基置換はミスセンス変異ではなくスプライシング変異である
    青砥 悠哉, 堀之内 智子, 近藤 淳, 永井 貞之, 榊原 菜々, 野津 寛大
    (一社)日本腎臓学会, Sep. 2021, 日本腎臓学会誌, 63(6-W) (6-W), 830 - 830, Japanese

  • 早期の遺伝学的検査が治療方針の選択に有用であった小児ステロイド抵抗性ネフローゼの1例
    近藤 淳, 堀之内 智子, 永井 貞之, 青砥 悠哉, 榊原 菜々, 野津 寛大
    (一社)日本腎臓学会, Sep. 2021, 日本腎臓学会誌, 63(6-W) (6-W), 833 - 833, Japanese

  • 極低出生体重児におけるビオチンおよびビオチン関連代謝産物の推移
    坊 亮輔, 山田 健治, 洪 聖媛, 南部 静紀, 藤岡 一路, 小林 弘典, 長谷川 有紀, 渡邊 敏明, 野津 寛大, 粟野 宏之
    (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 131 - 131, Japanese

  • 腎生検にてmedullary dysplasiaが示唆されたADTKD-HNF1βの一例
    中山 祐樹, 大庭 悠貴, 井熊 大輔, 水野 裕基, 山内 真之, 諏訪部 達也, 河野 圭, 大橋 健一, 山口 裕, 野津 寛大, 乳原 善文, 澤 直樹
    (一社)日本腎臓学会, Sep. 2021, 日本腎臓学会誌, 63(6-E) (6-E), 675 - 675, Japanese

  • COL4A4遺伝子変異による常染色体優性アルポート症候群の1例
    大久保 直人, 井熊 大輔, 大庭 悠貴, 水野 裕基, 山内 真之, 諏訪部 達也, 乳原 喜文, 河野 圭, 大橋 健一, 野津 寛大, 澤 直樹
    (一社)日本腎臓学会, Sep. 2021, 日本腎臓学会誌, 63(6-E) (6-E), 723 - 723, Japanese

  • 極低出生体重児におけるビオチンおよびビオチン関連代謝産物の推移
    坊 亮輔, 山田 健治, 洪 聖媛, 南部 静紀, 藤岡 一路, 小林 弘典, 長谷川 有紀, 渡邊 敏明, 野津 寛大, 粟野 宏之
    (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 131 - 131, Japanese

  • Jumpei Kuroda, Ryoko Harada, Riku Hamada, Yusuke Okuda, Yasuhiro Yoshida, Hiroshi Hataya, Kandai Nozu, Kazumoto Iijima, Masataka Honda, Kenji Ishikura
    BACKGROUND: In typical cases of Bartter syndrome (BS), assessing response to diuretics (furosemide and thiazide), hereinafter referred to as diuretic loading test, may be used to diagnose the type by detecting which part of the kidney tubule is not functioning correctly. However, the diuretic loading test may not always agree with the results of genetic analyses. CASE PRESENTATION: A 5-year-old boy was admitted due to lower extremity weakness and abnormal gait. He had a recurrent episode of muscle weakness and laboratory results showed severe hypokalemia. The direct genomic sequencing of the case revealed a new mutation in the SLC12A1 gene, which is associated with type I Bartter syndrome. Because there was the difference between the phenotype and genotype, we conducted a diuretic loading test to confirm the diagnosis. However, the results showed a clear increase in urine excretion of Na and Cl. These results were not consistent with typical type I BS, but consistent with the patient's phenotype. CONCLUSION: The diuretic loading test has limited utility for diagnosis especially in atypical cases. On the other hand, this test, which allows assessment of channel function, is useful for better understanding of the genotype-phenotype correlation.
    Aug. 2021, BMC nephrology, 22(1) (1), 295 - 295, English, International magazine
    Scientific journal

  • Atsushi Kondo, China Nagano, Shinya Ishiko, Takashi Omori, Yuya Aoto, Rini Rossanti, Nana Sakakibara, Tomoko Horinouchi, Tomohiko Yamamura, Sadayuki Nagai, Eri Okada, Yuko Shima, Koichi Nakanishi, Takeshi Ninchoji, Hiroshi Kaito, Hiroki Takeda, Hiroaki Nagase, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    Gitelman syndrome is an autosomal recessive inherited salt-losing tubulopathy. It has a prevalence of around 1 in 40,000 people, and heterozygous carriers are estimated at approximately 1%, although the exact prevalence is unknown. We estimated the predicted prevalence of Gitelman syndrome based on multiple genome databases, HGVD and jMorp for the Japanese population and gnomAD for other ethnicities, and included all 274 pathogenic missense or nonsense variants registered in HGMD Professional. The frequencies of all these alleles were summed to calculate the total variant allele frequency in SLC12A3. The carrier frequency and the disease prevalence were assumed to be twice and the square of the total allele frequency, respectively, according to the Hardy-Weinberg principle. In the Japanese population, the total carrier frequencies were 0.0948 (9.5%) and 0.0868 (8.7%) and the calculated prevalence was 0.00225 (2.3 in 1000 people) and 0.00188 (1.9 in 1000 people) in HGVD and jMorp, respectively. Other ethnicities showed a prevalence varying from 0.000012 to 0.00083. These findings indicate that the prevalence of Gitelman syndrome in the Japanese population is higher than expected and that some other ethnicities also have a higher prevalence than has previously been considered.
    Aug. 2021, Scientific reports, 11(1) (1), 16099 - 16099, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Bilateral Renal Hypoplasia with High β2-Microglobulinuria in the Neonatal Period.
    Sadayuki Nagai, Kazumichi Fujioka, Shogo Minamikawa, Kandai Nozu, Kazumoto Iijima
    Urinary β2 microglobulin (β2-MG) is a low-molecular-weight protein that is filtered by the glomerular basement membrane and absorbed by the proximal tubule epithelial cells. In perinatal management, urinary β2-MG levels are used to assess intrauterine inflammation in newborns, since urinary excretion increases during inflammation. Furthermore, β2-MG levels in fetal blood and urine are also used for predicting fetal renal function because β2-MG is not transferred to the placenta. Herein, we reported a patient with persistent high urinary β2-MG levels since neonatal period, who was later diagnosed with bilateral renal hypoplasia. If a newborn presents persistent hyper β2-microglobulinuria even without hematuria or proteinuria, congenital renal malformations should be considered.
    Aug. 2021, The Kobe journal of medical sciences, 67(1) (1), E34-E37, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yusuke Ishida, Masahiro Nishiyama, Hiroshi Yamaguchi, Kazumi Tomioka, Hiroki Takeda, Shoichi Tokumoto, Daisaku Toyoshima, Azusa Maruyama, Yusuke Seino, Kazunori Aoki, Kandai Nozu, Hiroshi Kurosawa, Ryojiro Tanaka, Kazumoto Iijima, Hiroaki Nagase
    ABSTRACT: Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels.We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy.Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier.Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition.
    Jul. 2021, Medicine, 100(30) (30), e26660, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomokazu Kimizu, Shinobu Ida, Kentaro Okamoto, Hiroyuki Awano, Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Shin Okazaki, Hideki Shimomura, Tomoko Lee, Koji Tominaga, Shin Nabatame, Toshio Saito, Takashi Hamazaki, Norio Sakai, Kayoko Saito, Haruo Shintaku, Kandai Nozu, Yasuhiro Takeshima, Kazumoto Iijima, Hisahide Nishio, Masakazu Shinohara
    Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. The severe form of SMA is among the genetic diseases with the highest infant mortality. Although SMA has been considered incurable, newly developed drugs-nusinersen and onasemnogene abeparvovec-improve the life prognoses and motor functions of affected infants. To maximize the efficacy of these drugs, treatments should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is now strongly recommended. Herein, we provide some data based on our experience of SMA diagnosis by genetic testing in Japan. A total of 515 patients suspected of having SMA or another lower motor neuron disease were tested. Among these patients, 228 were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. We analyzed the distribution of clinical subtypes and ages at genetic testing in the SMN1-deleted patients, and estimated the SMA incidence based on data from Osaka and Hyogo prefectures, Japan. Our data showed that confirmed diagnosis by genetic testing was notably delayed, and the estimated incidence was 1 in 30,000-40,000 live births, which seemed notably lower than in other countries. These findings suggest that many diagnosis-delayed or undiagnosed cases may be present in Japan. To prevent this, newborn screening programs for SMA (SMA-NBS) need to be implemented in all Japanese prefectures. In this article, we also introduce our pilot study for SMA-NBS in Osaka Prefecture.
    Jul. 2021, International journal of neonatal screening, 7(3) (3), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshihiko Ikuta, Shinya Abe, Shutaro Suga, Ruka Nakasone, Mariko Ashina, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka
    The incidence of syphilis infection among pregnant women is persistently high in Japan and in several developed countries. Here, we report the utility of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection. Because the recommended treatment (intramuscular benzathine benzylpenicillin) is not available in Japan, we intravenously administered benzylpenicillin for 10 days, which is used for treatment in high-risk cases. The administration of benzylpenicillin in low-risk infants resulted in an extended duration of parent-to-infant separation and increased the infants' exposure to invasive procedures. Thus, establishing evidence of the adequacy of no-treatment follow-up in low-risk groups and introducing intramuscular injections of benzathine benzylpenicillin may improve the management of infants suspected with congenital syphilis in Japan.
    Jul. 2021, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 27(11) (11), 1662 - 1664, English, International magazine
    Scientific journal

  • 学校検診で発見されたdense deposit diseaseの1例
    加古 優香, 神吉 直宙, 野津 寛大, 飯島 一誠, 澤井 俊宏, 吉川 徳茂, 久呉 真章
    Dense deposit disease(DDD)は、小児期に発症するまれな糸球体疾患であり、治療法はまだ確立していない。学校検尿を契機に診断されたdense deposit diseaseの1例を報告する。症例は15歳女児。11歳の時、学校検診で蛋白尿と血尿を指摘され、当院を紹介受診した。初診時、腎機能障害はなく、C3 20mg/dL、C4 14mg/dL、CH50 15U/mLと低補体血症を認めた。腎生検において、蛍光抗体法でC3単独の沈着、電子顕微鏡像で基底膜内にソーセージ様の高電子密度沈着物を認め、DDDと診断した。抗H因子抗体やC3NeFは陰性であり、次世代シークエンサーを用いた遺伝子解析では補体関連遺伝子異常を認めなかった。ステロイドによる治療で寛解し、血清C3値も正常化した。遺伝子変異のないDDDに対して、ステロイドによる治療が有効であった。(著者抄録)
    日本小児腎不全学会, Jul. 2021, 日本小児腎不全学会雑誌, 41, 119 - 123, Japanese

  • Shinya Ishiko, Akihito Tanaka, Asami Takeda, Masayuki Hara, Naoto Hamano, Masahiro Koizumi, Toshinori Ueno, Hiroki Hayashi, Atsushi Kondo, Sadayuki Nagai, Yuya Aoto, Nana Sakakibara, China Nagano, Tomoko Horinouchi, Tomohiko Yamamura, Takeshi Ninchoji, Yuko Shima, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy. METHODS: We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases. RESULTS: Four of the cases were genetically diagnosed with Alport syndrome (Cases 1-4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1-4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed. CONCLUSION: Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.
    Jul. 2021, Clinical and experimental nephrology, 25(7) (7), 779 - 787, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Rini Rossanti, Kandai Nozu, Atsushi Fukunaga, China Nagano, Tomoko Horinouchi, Tomohiko Yamamura, Nana Sakakibara, Shogo Minamikawa, Shinya Ishiko, Yuya Aoto, Eri Okada, Takeshi Ninchoji, Noritoshi Kato, Shoichi Maruyama, Keiji Kono, Shinichi Nishi, Kazumoto Iijima, Hideki Fujii
    BACKGROUND: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. METHODS: We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. Fabry Stabilization Index was used to determine the clinical severity. RESULTS: Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%). CONCLUSION: We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.
    Jun. 2021, Clinical and experimental nephrology, 25(11) (11), 1224 - 1230, English, Domestic magazine
    Scientific journal

  • 石森 真吾, 藤村 順也, 堀之内 智子, 山村 智彦, 榊原 菜々, 長野 智那, 西田 浩輔, 藤岡 一路, 忍頂寺 毅史, 野津 寛大
    日本小児泌尿器科学会, Jun. 2021, 日本小児泌尿器科学会雑誌, 30(2) (2), 202 - 202, Japanese

  • 小児から成人へのシームレスなネフローゼ診療 単一遺伝子異常と小児および成人におけるネフローゼ症候群
    堀之内 智子, 野津 寛大, 長野 智那, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 396 - 396, Japanese

  • ゲノムデータベースに基づく民族によるGitelman症候群の推定有病率の検討
    近藤 淳, 野津 寛大, 永井 貞之, 青砥 悠哉, Rini Rosanti, 榊原 菜々, 長野 智那, 堀之内 智子, 忍頂寺 毅史, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 435 - 435, Japanese

  • COL4A5遺伝子collagenous domain内のnon-Glyミスセンス変異によるX染色体連鎖型Alport症候群発症メカニズムの解明
    青砥 悠哉, 野津 寛大, 近藤 淳, 永井 貞之, Rini Rosanti, 榊原 菜々, 長野 智那, 堀之内 智子, 忍頂寺 毅史, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 456 - 456, Japanese

  • Oxford分類による小児IgA腎症(IgAN)、紫斑病性腎炎(IgAVN)の臨床病理学的検討
    島 友子, 浜 武継, 向山 弘展, 田中 侑, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂, 中西 浩一
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 444 - 444, Japanese

  • CLCN5遺伝子を含むX染色体微細欠失により発症したDent disease-1女性の2例
    榊原 菜々, 野津 寛大, 青砥 悠哉, 長野 智那, 堀之内 智子, 忍頂寺 毅史, 岡田 絵里, 川口 武彦, 今澤 俊之, 稲垣 徹史, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 456 - 456, Japanese

  • 米井 歩, 酒井 規夫, 野津 寛大, 永井 真理子, 佐藤 友紀, 望月 秀樹
    (一社)日本遺伝カウンセリング学会, Jun. 2021, 日本遺伝カウンセリング学会誌, 42(2) (2), 102 - 102, Japanese

  • Kentaro Nishi, Koichi Kamei, Masao Ogura, Mai Sato, Sho Ishiwa, Yoko Shioda, Chikako Kiyotani, Kimikazu Matsumoto, Kandai Nozu, Kenji Ishikura, Shuichi Ito
    BACKGROUND: Although hypotension is a life-threatening complication of nephrectomy in children, risk factors for its development remain unknown. We evaluated the incidence, clinical course, and associated risk factors of pediatric post-nephrectomy hypotension in an observational study. METHODS: This retrospective observational study included the clinical data of children who underwent nephrectomy in our center between 2002 and 2020. Patients undergoing nephrectomy at kidney transplantation and those who developed hypotension before nephrectomy were excluded. RESULTS: The study included 55 nephrectomies in 51 patients, including 42 unilateral, 4 two-stage bilateral, and 5 simultaneous bilateral nephrectomies. The diagnoses were isolated Wilms tumor, neuroblastoma, congenital nephrotic syndrome, Denys-Drash syndrome, WAGR (Wilms tumor, aniridia, genitourinary malformations, and mental retardation) syndrome, and autosomal recessive polycystic kidney disease in 24, 10, 9, 6, 1, and 1 patient, respectively. Post-nephrectomy hypotension developed in 11 (20%) patients. Two patients (3.6%) had persistent hypotension; both had their kidneys resected, and one patient (1.8%) died. Male sex, kidney disease, resection of both kidneys, low estimated glomerular filtration rate, increased left ventricular posterior wall thickness in diastole, hypertension before nephrectomy, antihypertensive use, hyperreninemia, and hyperaldosteronism were significantly associated with post-nephrectomy hypotension. Multivariate logistic regression analysis revealed that hypertension before nephrectomy was the only significant risk factor for post-nephrectomy hypotension (P = 0.04). CONCLUSIONS: Hypertension before nephrectomy is a significant risk factor for pediatric post-nephrectomy hypotension. Life-threatening hypotension, which might occur after bilateral nephrectomy in infants, should be considered, especially in children with higher risks.
    May 2021, Pediatric nephrology (Berlin, Germany), 36(11) (11), 3699 - 3709, English, International magazine
    Scientific journal

  • 堀之内 智子, 山村 智彦, 永井 貞之, 近藤 淳, 青砥 悠哉, 榊原 菜々, 長野 智那, 忍頂寺 毅史, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 92 - 92, Japanese

  • 青砥 悠哉, 高岡 裕, 近藤 淳, 永井 貞之, 岡田 絵里, Rossanti Rini, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 忍頂寺 毅史, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 92 - 92, Japanese

  • 近藤 淳, 野津 寛大, 永井 貞之, 青砥 悠哉, Rossanti Rini, 榊原 菜々, 長野 智那, 堀之内 智子, 忍頂寺 毅史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 98 - 98, Japanese

  • 榊原 菜々, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rossanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 忍頂寺 毅史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 126 - 126, Japanese

  • 忍頂寺 毅史, 堀之内 智子, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 石森 真吾, 藤村 順也, 神吉 直宙, 貝藤 裕史, 田中 亮二郎, 島 友子, 中西 浩一, 吉川 徳茂, 飯島 一誠, 野津 寛大
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 111 - 111, Japanese

  • 永井 貞之, 堀之内 智子, 近藤 淳, 青砥 悠哉, 榊原 菜々, 忍頂寺 毅史, 石森 真吾, 藤村 順也, 神吉 直宙, 貝藤 裕史, 田中 亮二郎, 島 友子, 中西 浩一, 吉川 徳茂, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 112 - 112, Japanese

  • 島 友子, 向山 弘展, 田中 侑, 和田 卓三, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂, 中西 浩一
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 113 - 113, Japanese

  • 津川 浩二, 橋本 峻, 佐藤 理子, 相澤 知美, 渡邊 祥二郎, 田中 完, 長野 智那, 野津 寛大, 城 謙輔
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 148 - 148, Japanese

  • China Nagano, Yutaka Takaoka, Koichi Kamei, Riku Hamada, Daisuke Ichikawa, Kazuki Tanaka, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, Eri Okada, Tomoko Horinouchi, Tomohiko Yamamura, Yurika Tsuji, Yuko Noguchi, Shingo Ishimori, Hiroaki Nagase, Takeshi Ninchoji, Kazumoto Iijima, Kandai Nozu
    INTRODUCTION: WT1 missense mutation in exon 8 or 9 causes infantile nephrotic syndrome with early progression to end-stage kidney disease (ESKD), Wilms tumor, and 46,XY female. However, some patients with missense mutations in exon 8 or 9 progress to ESKD in their teens or later. Therefore, we conducted a systematic review and functional analysis of WT1 transcriptional activity. METHODS: We conducted a systematic review of 174 cases with WT1 exon 8 or 9 missense variants from our cohort (n=13) and previous reports (n=161). Of these cases, mild and severe genotypes were selected for further in vitro functional analysis using luciferase assay. RESULTS: The median age of developing ESKD was 1.17 years. A comparative study was conducted among three WT1 genotype classes: mutations of the DNA-binding site (DBS group), mutations outside the DNA-binding site but at sites important for zinc finger structure formation by 2 cysteines and 2 histidines (C2H2 group), and mutations leading to other amino acid changes (Others group). The DBS group showed the severest phenotype and the C2H2 group was intermediate, whereas the Others group showed the mildest phenotype (developing ESKD at 0.90, 2.00, and 3.92 years, respectively, with significant differences). In vitro functional analysis showed dominant-negative effects for all variants; in addition, the DBS and C2H2 mutations were associated with significantly lower WT1 transcriptional activity than the other mutations. CONCLUSION: Not only the DNA-binding site but also C2H2 zinc finger structure sites are important for maintaining WT1 transcriptional activity, and their mutation causes severe clinical symptoms.
    Elsevier BV, May 2021, Kidney International Reports, 6(8) (8), 2114 - 2121, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yu Tanaka, Naoya Morisada, Tomohiro Suzuki, Yoshitaka Ohashi, Ming Juan Ye, Kandai Nozu, Satoru Tsuruta, Kazumoto Iijima
    We present a female patient with a dual genetic diagnosis of autosomal dominant tubulointerstitial kidney disease and KBG syndrome. The proband was an 18-year-old woman presenting with intellectual disability, renal insufficiency, and hyperuricemia. Abdominal ultrasonography did not reveal any abnormalities. The patient's father had been diagnosed with chronic kidney disease and hyperuricemia in his twenties; however, he had no intellectual disability. Her mother and two younger siblings were not affected. Next generation sequencing (NGS) identified mutations in UMOD (c.796T > C) of the proband and her father, and in ANKRD11 (c.1903_1907del) of the proband. Renal insufficiency and intellectual disability were attributed to mutations in UMOD and ANRKD11, respectively. When making genetic diagnoses, the presence of multiple mutations in an individual should be considered, particularly when not all symptoms could be attributed to a single disease. The number of patients with dual genetic diagnosis is expected to increase as NGS becomes more readily available; thus, making it necessary to undertake a careful and robust assessment of the clinical symptoms and the related genotypes, to ensure an accurate diagnosis.
    May 2021, CEN case reports, 10(2) (2), 184 - 188, English, Domestic magazine
    Scientific journal

  • Masahiro Nishiyama, Yusuke Ishida, Hiroshi Yamaguchi, Shoichi Tokumoto, Kazumi Tomioka, Hiroto Hongo, Daisaku Toyoshima, Azusa Maruyama, Hiroshi Kurosawa, Ryojiro Tanaka, Kandai Nozu, Kazumoto Iijima, Hiroaki Nagase
    OBJECTIVE: The clinical prediction rule (CPR) for acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was developed with an area under the receiver operating characteristic curve (AUC) of 0.95 - 0.96. Our objective was to verify the AESD CPR in a new cohort and compare the utilities of three CPRs of acute encephalopathy: the Tada, Yokochi, and Nagase criteria. METHODS: We reviewed the clinical data and medical charts of 580 consecutive patients (aged < 18 years) with febrile convulsive status epilepticus lasting for ≥ 30 min in 2002 - 2017 and measured the performance of the CPRs in predicting AESD and sequelae. RESULTS: The CPRs predicted AESD with an AUC of 0.84 - 0.88. The Tada criteria predicted AESD with a positive predictive value (PPV) of 0.25 and a negative predictive value (NPV) of 0.99. The Yokochi criteria predicted AESD with a PPV and NPV of 0.20 and 0.95, respectively, after 12 h. The Nagase criteria predicted AESD with a PPV and NPV of 0.14 and 1.00, respectively, after 6 h. The PPVs of the Tada, Yokochi, and Nagase criteria for sequelae were 0.28, 0.28, and 0.17, respectively; the corresponding NPVs were 0.97, 0.95, and 0.98, respectively. CONCLUSIONS: The effectiveness of the AESD CPR in a new cohort was lower than that in the derivation study. CPRs are not sufficient as diagnostic tests, but they are useful as screening tests. The Nagase criteria are the most effective for screening among the three CPRs due to their high NPV and swiftness.
    May 2021, Brain & development, 43(5) (5), 616 - 625, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomohiko Inoue, China Nagano, Masafumi Matsuo, Tomohiko Yamamura, Nana Sakakibara, Tomoko Horinouchi, Yugo Shibagaki, Daisuke Ichikawa, Yuya Aoto, Shinya Ishiko, Shingo Ishimori, Rini Rossanti, Kazumoto Iijima, Kandai Nozu
    May 2021, Clinical and experimental nephrology, 25(5) (5), 564 - 564, English, Domestic magazine

  • Hiroaki Hanafusa, Yoshihiko Hidaka, Tomomi Yamaguchi, Hisashi Shimojo, Takanori Tsukahara, Tsubasa Murase, Daisuke Matsuoka, Nao Chiba, Shun Shimada, Hirokazu Morokawa, Norio Omori, Hironori Minoura, China Nagano, Kyoko Takano, Katsuya Nakamura, Keiko Wakui, Yoshimitsu Fukushima, Takeshi Uehara, Yozo Nakazawa, Kazumoto Iijima, Kandai Nozu, Tomoki Kosho
    Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.
    Apr. 2021, American journal of medical genetics. Part A, 185(7) (7), 2175 - 2179, English, International magazine

  • Elena Bonora, Sanjiban Chakrabarty, Georgios Kellaris, Makiko Tsutsumi, Francesca Bianco, Christian Bergamini, Farid Ullah, Federica Isidori, Irene Liparulo, Chiara Diquigiovanni, Luca Masin, Nicola Rizzardi, Mariapia Giuditta Cratere, Elisa Boschetti, Valentina Papa, Alessandra Maresca, Giovanna Cenacchi, Rita Casadio, Pierluigi Martelli, Ivana Matera, Isabella Ceccherini, Romana Fato, Giuseppe Raiola, Serena Arrigo, Sara Signa, Angela Rita Sementa, Mariasavina Severino, Pasquale Striano, Chiara Fiorillo, Tsuyoshi Goto, Shumpei Uchino, Yoshinobu Oyazato, Hisayoshi Nakamura, Sushil K Mishra, Yu-Sheng Yeh, Takema Kato, Kandai Nozu, Jantima Tanboon, Ichiro Morioka, Ichizo Nishino, Tatsushi Toda, Yu-Ichi Goto, Akira Ohtake, Kenjiro Kosaki, Yoshiki Yamaguchi, Ikuya Nonaka, Kazumoto Iijima, Masakazu Mimaki, Hiroki Kurahashi, Anja Raams, Alyson MacInnes, Mariel Alders, Marc Engelen, Gabor Linthorst, Tom de Koning, Wilfred den Dunnen, Gerard Dijkstra, Karin van Spaendonck, Dik C van Gent, Eleonora M Aronica, Paolo Picco, Valerio Carelli, Marco Seri, Nicholas Katsanis, Floor A M Duijkers, Mariko Taniguchi-Ikeda, Roberto De Giorgio
    Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities. Bonora et al. identify a new mitochondrial recessive disorder caused by biallelic variants in the LIG3 gene encoding DNA ligase III, which is responsible for mitochondrial DNA repair. Clinical signs include gut dysmotility and neurological features such as leucoencephalopathy, epilepsy and stroke-like episodes.
    Apr. 2021, Brain : a journal of neurology, 144(5) (5), 1451 - 1466, English, International magazine
    Scientific journal

  • Hiroshi Yamaguchi, Kandai Nozu, Shinya Ishiko, Hiroaki Nagase, Takeshi Ninchoji, China Nagano, Hiroki Takeda, Ai Unzaki, Kazuto Ishibashi, Ichiro Morioka, Kazumoto Iijima, Akihito Ishida
    OBJECTIVES: To examine the association between the number of visits to the emergency department (ED) by children for night-time headaches and exposure to multifaceted factors, such as meteorological conditions and air pollution. DESIGN: We conducted a clinical observational time-series analysis study. SETTING: We reviewed consecutive patients younger than 16 years of age at the primary ED centre in Kobe city, Japan, during the night shift (19:30-7:00 hours) between 1 January 2011 and 31 December 2019. PARTICIPANTS: In total, 265 191 children visited the ED; 822 presented with headache during the study period. PRIMARY OUTCOME MEASURES: We investigated the effects of meteorological factors and air pollutants by multivariate analysis of Poisson regression estimates. A subanalysis included the relationship between the number of patients with night-time headaches and the above factors by sex. Furthermore, the effect of typhoon landing on patient visits for headache was also analysed. Headache was not classified because examinations were performed by general paediatricians (non-specialists). RESULTS: The number of patients with night-time headaches displayed distinct seasonal changes, with peaks during the summer. Multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients for headache and mean temperature. Subanalysis by sex indicated a positive relationship between the number of patients with headache and mean temperature in both sexes; however, it was significant only for females. No relationship was found between the number of patients with headache and air pollution. There was no change in the number of patients for night-time headaches 3 days before and after typhoon landing. CONCLUSIONS: High temperature is the main factor for visiting ED for night-time headaches among children in Kobe city. Our results suggest that preventive measures against night-time headaches may be possible by reducing time spent outside during summer.
    Apr. 2021, BMJ open, 11(4) (4), e046520, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 榊原 菜々, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rossanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 田中 亮二郎, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2021, 日本小児腎臓病学会雑誌, 34(1) (1), 87 - 87, Japanese

  • 長野 智那, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2021, 日本小児腎臓病学会雑誌, 34(1) (1), 91 - 91, Japanese

  • 榊原 菜々, 岡本 孝之, 野津 寛大, 佐藤 泰征, 林 麻子, 高橋 俊行, 上田 泰弘, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rossanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2021, 日本小児腎臓病学会雑誌, 34(1) (1), 93 - 93, Japanese

  • Yuko Shima, Koichi Nakanishi, Hironobu Mukaiyama, Yu Tanaka, Takuzo Wada, Ryojiro Tanaka, Hiroshi Kaito, Kandai Nozu, Mayumi Sako, Kazumoto Iijima, Norishige Yoshikawa
    BACKGROUND: IgA nephropathy (IgAN) is characterized by predominant mesangial IgA deposition. Some patients with IgAN demonstrate IgA deposition in glomerular peripheral capillaries (cap-IgA). The clinicopathological significance of cap-IgA remains incompletely investigated in children. METHODS: We retrospectively analyzed 503 consecutive cases of biopsy-proven childhood IgAN between July 1976 and June 2013 to compare clinical and pathological features between IgAN patients with and without cap-IgA. RESULTS: Among the 503 patients, 30 (6.0%) had cap-IgA. We found significant differences in proteinuria (2.0 vs. 0.5 g/day/m2, p < 0.0001), time from onset to kidney biopsy (2.2 vs. 8.3 months, p < 0.0001), and rate of proteinuria remission after treatment (23.3% vs. 48.0%, p = 0.007) between both groups. Pathological analysis revealed significant differences in M1 (83.3% vs. 56.0%, p = 0.002), ratio of subendothelial electron dense deposits (EDDs, 58.6% vs. 16.5%, p < 0.0001) and subepithelial EDDs (48.3% vs. 16.5%, p = 0.0001), and glomerular basement membrane (GBM) lysis (58.6% vs. 27.1%, p = 0.0006) between both groups. More than half of cap-IgA patients (17/30, 56.7%), whereas only 26.2% of non-cap-IgA patients (124/473), were treated with immunosuppressive treatments. Six of 30 cases (20%) with cap-IgA reached glomerular filtration rate (GFR) categories G3a-G5 (estimated GFR < 60 ml/min/1.73 m2) at most recent observation (mean observation period: 7.0 ± 4.0 years). According to Kaplan-Meier analysis, patients with cap-IgA had significantly lower kidney survival curves than non-cap-IgA patients (72.8% vs. 97.2% at 10 years, p < 0.0001). CONCLUSIONS: Cap-IgA is associated with acute inflammation with GBM changes, resulting in refractory heavier proteinuria. Cap-IgA may represent a poor prognostic factor.
    Apr. 2021, Pediatric nephrology (Berlin, Germany), 36(4) (4), 899 - 908, English, International magazine
    Scientific journal

  • Tomoko Horinouchi, Kaori Maeyama, Masashi Nagai, Masami Mizobuchi, Yasuko Takagi, Yuka Okada, Takeshi Kato, Mio Nishimura, Yoko Kawasaki, Mieko Yoshioka, Satoshi Takada, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Sachiyo Fukushima, Kazumichi Fujioka, Kazumi Tomioka, Hiroaki Nagase, Kandai Nozu, Kazumoto Iijima, Noriyuki Nishimura
    Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.
    Mar. 2021, Journal of autism and developmental disorders, 52(2) (2), 483 - 489, English, International magazine
    Scientific journal

  • Satoru Takafuji, Takeshi Mori, Noriyuki Nishimura, Nobuyuki Yamamoto, Suguru Uemura, Kandai Nozu, Kiminori Terui, Tsutomu Toki, Etsuro Ito, Hideki Muramatsu, Yoshiyuki Takahashi, Masafumi Matsuo, Tomohiko Yamamura, Kazumoto Iijima
    Diamond-Blackfan anemia (DBA) is mainly caused by pathogenic variants in ribosomal proteins and 22 responsible genes have been identified to date. The most common causative gene of DBA is RPS19 [NM_001022.4]. Nearly 180 RPS19 variants have been reported, including three deep intronic variants outside the splicing consensus sequence (c.72-92A > G, c.356 + 18G > C, and c.411 + 6G > C). We also identified one case with a c.412-3C > G intronic variant. Without conducting transcript analysis, the pathogenicity of these variants is unknown. However, it is difficult to assess transcripts because of their fragility. In such cases, in vitro functional splicing assays can be used to assess pathogenicity. Here, we report functional splicing analysis results of four RPS19 deep intronic variants identified in our case and in previously reported cases. One splicing consensus variant (c.411 + 1G > A) was also examined as a positive control. Aberrant splicing with a 2-bp insertion between exons 5 and 6 was identified in the patient samples and minigene assay results also identified exon 6 skipping in our case. The exon 6 skipping transcript was confirmed by further evaluation using quantitative RT-PCR. Additionally, minigene assay analysis of three reported deep intronic variants revealed that none of them showed aberrant splicing and that these variants were not considered to be pathogenic. In conclusion, the minigene assay is a useful method for functional splicing analysis of inherited disease.
    Feb. 2021, Pediatric hematology and oncology, 38(6) (6), 1 - 16, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Rini Rossanti, Toshio Watanabe, China Nagano, Shigeo Hara, Tomoko Horinouchi, Tomohiko Yamamura, Nana Sakakibara, Takeshi Ninchoji, Kazumoto Iijima, Kandai Nozu
    The identification of monogenic causes in patients with proteinuria has revealed that the encoded proteins functionally participate in distinct cellular tasks and signaling pathways in the slit diaphragms of the glomerular basement membrane. FAT1 is a member of a small family of vertebrate-cadherin-like genes, which is a crucial component in slit diaphragms and has a vital role in tubular regeneration. Only 5 cases with glomerulonephritis having FAT1 gene biallelic variants have been reported. However, only one had the biallelic truncating variant, and others had missense variants. Therefore, we need further evidence of this gene being responsible for steroid-resistant nephrotic syndrome (SRNS) or glomerulonephritis. Here we describe a 5-year-old boy in who proteinuria was detected at the age of 3 years without any extrarenal symptom. The pathological findings were examined, and targeted exome sequencing was performed. We also conducted reviews for all previously-reported cases of glomerulonephritis possessing FAT1 biallelic gene variants. We found two novel truncating variants in FAT1 (NM_005245.3), c.12867dup in exon 10, and, c.5480_5483del in exon 25. Our case showed mild proteinuria compared to previously-reported cases who showed SRNS and extrarenal symptoms that might have been because the latter variant in our patient was located on out of cadherin domains; however, our follow up period is short and we further need careful follow up. Our findings corroborate the evidence that individuals with FAT1-truncating variants can show isolated mild proteinuria. Further studies are needed to investigate the genotype-phenotype correlation in this disease. Therefore, our case will provide vital information regarding this rare condition.
    Feb. 2021, CEN case reports, 10(1) (1), 100 - 105, English, Domestic magazine
    Scientific journal

  • Ruka Nakasone, Kazumichi Fujioka, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Motoichiro Sakurai, Katsumi Mizuno, Kandai Nozu, Kazumoto Iijima
    We report a case of a preterm infant who developed cow's milk allergy. This male infant presented with recurrent ascites and was successfully treated with donated breast milk. He was born at 24 weeks' gestation with a birthweight of 506 g. From day 20, infant formula, soy protein-based formula, and casein-hydrolyzed formula were used due to insufficient maternal lactation. This resulted in abdominal distention, generalized edema, and recurrent ascites. We diagnosed him with cow's milk allergy since these symptoms improved on exclusive breast milk feeding. No recurrence of symptoms occurred when donated breast milk was used in combination with the mother's own milk. Ascites should be regarded as a clinical symptom of neonatal cow's milk allergy. Donated breast milk may be effective in the treatment of the allergy if breastfeeding is not available.
    Jan. 2021, International journal of environmental research and public health, 18(3) (3), English, International magazine
    Link to Kobe Univ. Repository (Kernel)

  • Koji Sakuraya, Kandai Nozu, Hitohiko Murakami, China Nagano, Tomoko Horinouchi, Shuichiro Fujinaga, Kazumoto Iijima, Yoshiyuki Ohtomo
    Biallelic pathogenic variants in the laminin β2 (LAMB2) gene, which encodes laminin β2, are associated with Pierson syndrome characterized by a congenital nephrotic syndrome that rapidly progresses to end-stage renal disease, distinct ocular maldevelopment with bilateral microcoria, and neurodevelopmental deficits. However, the phenotypic spectrum of LAMB2-associated disorder is broader than expected, and cases with milder phenotypes such as isolated congenital or infantile nephrotic syndrome have also been reported. We report a patient with LAMB2-associated renal disorder showing an extremely mild phenotype. A 5-year-old girl presented with asymptomatic proteinuria and hematuria detected by urinalysis screening. She had been previously healthy without any additional renal symptoms. The serum albumin and creatinine levels were normal. Renal biopsy revealed minor glomerular abnormalities with occasional focal mesangial proliferation. Electron microscopy showed no structural changes in the glomerular basement membrane. Targeted sequencing of podocyte-related genes using next-generation sequencing was performed. As a result, previously reported biallelic pathogenic variants of the truncating variant (c.5073_5076dupCCAG) and a splice site variant (c.3797 + 5G > A) in the LAMB2 gene were detected, and the patient was diagnosed with LAMB2-associated renal disorder. Interestingly, a previously reported case with this splicing variant also showed an atypically mild phenotype. We suggest that clinicians should consider LAMB2-associated nephritis as an important differential diagnosis in children with asymptomatic proteinuria and microscopic hematuria if there is no structural change in the glomerular basement membrane. A comprehensive gene-screening system using next-generation sequencing is useful for diagnosing these atypical cases with isolated urine abnormalities.
    Jan. 2021, CEN case reports, 10(3) (3), 359 - 363, English, Domestic magazine
    Scientific journal

  • Ruka Nakasone, Kazumichi Fujioka, Yuki Kyono, Asumi Yoshida, Takumi Kido, Shutaro Suga, Shinya Abe, Mariko Ashina, Kosuke Nishida, Kenji Tanimura, Hideto Yamada, Kandai Nozu, Kazumoto Iijima
    To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ <80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI.
    Jan. 2021, International journal of environmental research and public health, 18(2) (2), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 再生検にて糸球体硬化病変の著明な進行とともに蛍光抗体法の染色パターンの変化を呈した巣状分節性糸球体硬化症の一例
    副田 圭祐, 小泉 賢洋, 五十棲 このみ, 中川 洋佑, 濱野 直人, 小倉 豪, 野津 寛大, 新村 文男, 和田 健彦, 深川 雅史, 城 謙輔, 山口 裕
    日本ベーリンガーインゲルハイム(株), 2021, 腎炎症例研究, 38, 46 - 67, Japanese

  • 再生検にて糸球体硬化病変の著明な進行とともに蛍光抗体法の染色パターンの変化を呈した巣状分節性糸球体硬化症の一例
    副田 圭祐, 小泉 賢洋, 五十棲 このみ, 中川 洋佑, 濱野 直人, 小倉 豪, 野津 寛大, 新村 文男, 和田 健彦, 深川 雅史, 城 謙輔, 山口 裕
    日本ベーリンガーインゲルハイム(株), 2021, 腎炎症例研究, 38, 46 - 67, Japanese

  • Hiroshi Yamaguchi, Masahiro Nishiyama, Shoichi Tokumoto, Yusuke Ishida, Kazumi Tomioka, Kazunori Aoki, Yusuke Seino, Daisaku Toyoshima, Hiroki Takeda, Hiroshi Kurosawa, Hiroshi Sakuma, Hiroko Tada, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima, Hiroaki Nagase
    Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.
    Jan. 2021, Cytokine, 137, 155324 - 155324, English, International magazine
    Scientific journal

  • Ruka Nakasone, Kazumichi Fujioka, Kosuke Nishida, Kandai Nozu, Kazumoto Iijima
    Jan. 2021, Pediatrics and neonatology, 62(1) (1), 119 - 121, English, International magazine
    Link to Kobe Univ. Repository (Kernel)

  • Shutaro Suga, Kazumichi Fujioka, Ruka Nakasone, Shinya Abe, Sachiyo Fukushima, Mariko Ashina, Kosuke Nishida, Kandai Nozu, Kazumoto Iijima, Kenji Tanimura, Hideto Yamada
    This study aimed to investigate the long-term changes in awareness of and knowledge about mother-to-child infections across 6 years in Japan. A questionnaire survey was conducted at our facility from October 2012 to January 2018, and the study periods were divided into 4 phases comprising 16 months each. A multiple-choice questionnaire assessed participants' awareness of the following 13 pathogens of mother-to-child infections: cytomegalovirus (CMV), Toxoplasma gondii (T. gondii), hepatitis B virus, rubella virus, herpes simplex virus, parvovirus B19, hepatitis C virus, human immunodeficiency virus, human T cell leukemia virus type-1, measles virus, varicella-zoster virus, Chlamydia trachomatis, and Treponema pallidum. For the selected four pathogens (i.e., CMV, rubella virus, T. gondii, and parvovirus B19), the questionnaire also evaluated participants' knowledge of transmission routes, the most susceptible time of infection that could yield severe fetal disease during pregnancy, the maximum frequency of fetal infection in cases of maternal infection, and methods to prevent maternal infection. In total, 1433 pregnant Japanese women were included in this study. There was no secular change in awareness of the pathogens concerning mother-to-child infections over time, and we also clarified that the detailed knowledge of the four pathogens of typical mother-to-child infections did not improve. Since knowledge about methods to prevent maternal infection is still insufficient for all pathogens, further advocacy is required to prevent mother-to-child infections.
    2021, PloS one, 16(1) (1), e0244945, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Glenn M Chertow, Gerald B Appel, Sharon Andreoli, Sripal Bangalore, Geoffrey A Block, Arlene B Chapman, Melanie P Chin, Keisha L Gibson, Angie Goldsberry, Kazumoto Iijima, Lesley A Inker, Bertrand Knebelmann, Laura H Mariani, Colin J Meyer, Kandai Nozu, Megan O'Grady, Arnold L Silva, Peter Stenvinkel, Roser Torra, Bradley A Warady, Pablo E Pergola
    INTRODUCTION: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. METHODS: The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12-70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30-90 mL/min/1.73 m2, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values >200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. RESULTS: A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (n = 77) or placebo (n = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m2, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was -4.9 mL/min/1.73 m2 despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. DISCUSSION/CONCLUSION: CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.
    2021, American journal of nephrology, 52(3) (3), 180 - 189, English, International magazine
    Scientific journal

  • Kandai Nozu, Yutaka Takaoka, Hirofumi Kai, Minoru Takasato, Kensuke Yabuuchi, Tomohiko Yamamura, Tomoko Horinouchi, Nana Sakakibara, Takeshi Ninchoji, China Nagano, Kazumoto Iijima
    Alport syndrome (AS) is a progressive inherited kidney disease characterized by hearing loss and ocular abnormalities. There are three forms of AS depending on inheritance mode: X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, which encodes type IV collagen α5 chain, while ADAS and ARAS are caused by variants in COL4A3 or COL4A4, which encode type IV collagen α3 or α4 chain, respectively. In male XLAS or ARAS cases, end-stage kidney disease (ESKD) develops around a median age of 20 to 30 years old, while female XLAS or ADAS cases develop ESKD around a median age of 60 to 70 years old. The diagnosis of AS is dependent on either genetic or pathological findings. However, determining the pathogenicity of the variants detected by gene tests can be difficult. Recently, we applied the following molecular investigation tools to determine pathogenicity: 1) in silico and in vitro trimer formation assay of α345 chains to assess triple helix formation ability, 2) kidney organoids constructed from patients' induced pluripotent stem cells to identify α5 chain expression on the glomerular basement membrane, and 3) in vitro splicing assay to detect aberrant splicing to determine the pathogenicity of variants. In this review article, we discuss the genetic background and novel assays for determining the pathogenicity of variants. We also discuss the current treatment approaches and introduce exon skipping therapy as one potential treatment option.
    Dec. 2020, Kidney research and clinical practice, 39(4) (4), 402 - 413, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroshi Yamaguchi, Hiroaki Nagase, Shoichi Tokumoto, Kazumi Tomioka, Masahiro Nishiyama, Hiroki Takeda, Takeshi Ninchoji, China Nagano, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. In 1984, Scheinberg and Sternlieb estimated the prevalence of WD to be 1:30,000. However, recent epidemiological studies have reported increasing prevalence rates in different populations. The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases. METHODS: Multiple public databases were used. First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. Next, we investigated the allele frequencies of these 885 variants in Japanese individuals using the Human Genetic Variation Database (HGVD) and the Japanese Multi Omics Reference Panel (jMorp). RESULTS: Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, 0 and 3 splicing variants, and 0 and 2 small deletions were found in the HGVD and in jMorp, respectively. The total allele frequencies of the ATP7B mutations were 0.011 in the HGVD and 0.014 in the jMorp. According to these data, the carrier frequencies were 0.022 (2.2%) and 0.028 (2.8%), respectively, and patient frequencies were 0.000121 (1.21/10,000 individuals) and 0.000196 (1.96/10,000 individuals), respectively. CONCLUSION: This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. The calculated prevalence of WD was comparatively higher than that of previous reports, indicating previous underdiagnosis or the existence of less severe phenotypes.
    Dec. 2020, Pediatrics international : official journal of the Japan Pediatric Society, 63(8) (8), 918 - 922, English, International magazine
    Scientific journal

  • Takeshi Ninchoji, Junya Fujimura, Suguru Uemura, Nobuyuki Yamamoto, Kandai Nozu, Kazumoto Iijima
    Extranodal natural killer/T-cell lymphoma (ENKTL) is difficult to identify and diagnose appropriately. Positron emission tomography imaging is a crucial method that leads to precise diagnosis. A proper regimen including stem cell transplantation would possibly improve prognosis of advanced ENKTL.
    Dec. 2020, Clinical case reports, 8(12) (12), 3658 - 3660, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nana Sakakibara, China Nagano, Shinya Ishiko, Tomoko Horinouchi, Tomohiko Yamamura, Shogo Minamikawa, Yuko Shima, Koichi Nakanishi, Shingo Ishimori, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Dent disease is associated with low molecular weight proteinuria and hypercalciuria and caused by pathogenic variants in either of two genes: CLCN5 (Dent disease 1) and OCRL (Dent disease 2). It is generally not accompanied by extrarenal manifestations and it is difficult to distinguish Dent disease 1 from Dent disease 2 without gene testing. We retrospectively compared the characteristics of these two diseases using one of the largest cohorts to date. METHODS: We performed gene testing for clinically suspected Dent disease, leading to the genetic diagnosis of 85 males: 72 with Dent disease 1 and 13 with Dent disease 2. A retrospective review of the clinical findings and laboratory data obtained from questionnaires submitted in association with the gene testing was conducted for these cases. RESULTS: The following variables had significantly higher levels in Dent disease 2 than in Dent disease 1: height standard deviation score (height SDS), serum creatinine-based estimated GFR (Cr-eGFR) (median: 84 vs. 127 mL/min/1.73 m2, p < 0.01), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum lactate dehydrogenase (LDH), serum creatine phosphokinase (CK), serum potassium, serum inorganic phosphorus, serum uric acid, urine protein/creatinine ratio (median: 3.5 vs. 1.6 mg/mg, p < 0.01), and urine calcium/creatinine ratio. There were no significant differences in serum sodium, serum calcium, alkaline phosphatase (ALP), urine β2-microglobulin, incidence of nephrocalcinosis, and prevalence of intellectual disability or autism spectrum disorder. CONCLUSIONS: The clinical and laboratory features of Dent disease 1 and Dent disease 2 were shown in this study. Notably, patients with Dent disease 2 showed kidney dysfunction at a younger age, which should provide a clue for the differential diagnosis of these diseases.
    Dec. 2020, Pediatric nephrology (Berlin, Germany), 35(12) (12), 2319 - 2326, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomohiko Yamamura, Tomoko Horinouchi, China Nagano, Takashi Omori, Nana Sakakibara, Yuya Aoto, Shinya Ishiko, Koichi Nakanishi, Yuko Shima, Hiroaki Nagase, Hiroki Takeda, Rini Rossanti, Ming Juan Ye, Yoshimi Nozu, Shingo Ishimori, Takeshi Ninchoji, Hiroshi Kaito, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    Early kidney failure in the hereditary type IV collagen disease, Alport syndrome, can be delayed by renin-angiotensin inhibitors. However, whether all patients and all different genotypes respond equally well to this kidney-protective therapy remains unclear. Here, we performed a retrospective study on 430 patients with male X-linked Alport syndrome to examine the relationships among kidney prognosis, genotype, and treatment effect in a large cohort of Japanese patients. We analyzed the clinical features, genotype-phenotype correlation, and kidney survival period for patients treated with or without renin-angiotensin inhibitors. As a result, the median kidney survival period of patients in this cohort was found to be at 35 years with a strong genotype-phenotype correlation. The median age at the onset of end stage kidney disease (ESKD) significantly differed between patients treated with and without renin-angiotensin inhibitors (over 50 years versus 28 years, respectively). Moreover, these drugs delayed the onset of ESKD in patients with truncating variants for 12 years, extending the median age from 16 years to 28 years. Thus, our results confirmed a strong genotype-phenotype correlation in patients with male X-linked Alport syndrome. Additionally, it was suggested that renin-angiotensin inhibitors could significantly delay ESKD progression. Despite these therapies, patients with truncating variants developed ESKD at the median age of 28 years.
    Dec. 2020, Kidney international, 98(6) (6), 1605 - 1614, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshinori Araki, Azusa Kawaguchi, Nana Sakakibara, Yoshinobu Nagaoka, Tomohiko Yamamura, Tomoko Horinouchi, China Nagano, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    Alport syndrome (AS) is a progressive kidney disease. Male cases with X-linked AS (XLAS) are reported to develop end-stage kidney disease (ESKD) at the age of around 20-30 years. One risk factor for developing ESKD at a young age is a genotype of having truncating variants in the COL4A5 gene. However, to date, other such factors have remained unclear. Here, we describe a 15-year-old Japanese boy with XLAS who had a missense variant in the COL4A5 gene. He presented with gross hematuria, severe proteinuria, oliguria, systemic edema, body weight gain, and hypertension after pharyngitis. Blood examination showed kidney dysfunction, hypocomplementemia, and elevated antistreptolysin-O level. We diagnosed him with poststreptococcal acute glomerulonephritis (PSAGN) and he was stopped treatment by lisinopril, and received supportive treatment. However, he showed an unusual clinical course for PSAGN and, consequently, developed ESKD 15 months after the onset of PSAGN without recovery from the kidney dysfunction. This case showed that the onset of PSAGN can be a risk factor for AS patients to develop ESKD at a young age.
    Nov. 2020, CEN case reports, 9(4) (4), 418 - 422, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yuya Aoto, Tomoo Kise, Koichi Nakanishi, China Nagano, Tomoko Horinouchi, Tomohiko Yamamura, Shinya Ishiko, Nana Sakakibara, Yuko Shima, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    X-linked Alport syndrome (XLAS) is a progressive hereditary kidney disease caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain. To date, 11 cases having somatic mosaic variants in COL4A5 have been reported; however, all of them involved single-nucleotide variations (SNVs). Here, we report a female XLAS patient with somatic mosaicism identified by copy number variation (CNV) in COL4A5. The case was a 35-year-old female, the mother of the proband, whose only clinical symptom was hematuria. The proband, who was the son of this patient, was diagnosed with XLAS by gene testing, which showed a large hemizygous deletion from exon 3-51 in COL4A5 detected by next-generation sequencing and then confirmed by multiplex ligation-dependent probe amplification (MLPA). Then, MLPA analysis revealed that the female patient had the same deletion with only a 20% copy number reduction compared with a normal female control; she was thus diagnosed with XLAS with somatic mosaicism. CNVs in COL4A5 are relatively rare and, to the best of our knowledge, somatic mosaic variants with CNVs have never been reported. This case clearly featured a germline variant because the patient's son exhibited XLAS. This is thus the first case report on an XLAS patient having CNV in COL4A5 with somatic mosaicism. The obtained findings were very important for the genetic counseling of this family.
    Nov. 2020, CEN case reports, 9(4) (4), 431 - 436, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Koji Sakuraya, Kandai Nozu, Itsuhiro Oka, Shuichiro Fujinaga, China Nagano, Yoshiyuki Ohtomo, Kazumoto Iijima
    Mutations in SLC4A1, encoding the chloride-bicarbonate exchanger known as anion exchanger 1, have been reported as the sole genetic cause of autosomal dominant distal renal tubular acidosis (dRTA). This disorder is extremely rare and most patients show no clinical symptoms during childhood. Here, we report a case of an infant with early-onset autosomal dominant dRTA caused by SLC4A1 mutation p.Gly609Arg that is detected as a hot spot world widely. Despite the fact that the patient's mother and sister had the same SLC4A1 mutation, all family members presented different clinical courses. A 9-month-old boy was referred to our hospital because of insufficient body weight gain. At the initial visit, his height and weight were 68.2 cm (-1.0 SD) and 6.4 kg (-2.2SD) respectively. Metabolic acidosis with a normal serum anion gap and inappropriate alkaline urine were detected. Abdominal ultrasound indicated bilateral renal medullary high-echoic lesions which suspected nephrocalcinosis. The genetic test revealed a heterozygous mutation c.1825G > A (p.Gly609Arg) in SLC4A1 that directed his diagnosis of autosomal dominant dRTA. The genetic test was performed on the patient's family members, indicating that the same SLC4A1 mutation was detected in his mother and sister. His mother had nephrocalcinosis and metabolic acidosis at the age of 35 years. However, his sister had no clinical symptoms at the age of 6 years without any laboratory abnormalities. This familial case demonstrated that the significant heterogeneity in clinical manifestations may develop even among familial members sharing the same variant.
    Nov. 2020, CEN case reports, 9(4) (4), 442 - 445, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Xiaoyuan Jia, Tomohiko Yamamura, Rasheed Gbadegesin, Michelle T McNulty, Kyuyong Song, China Nagano, Yuki Hitomi, Dongwon Lee, Yoshihiro Aiba, Seik-Soon Khor, Kazuko Ueno, Yosuke Kawai, Masao Nagasaki, Eisei Noiri, Tomoko Horinouchi, Hiroshi Kaito, Riku Hamada, Takayuki Okamoto, Koichi Kamei, Yoshitsugu Kaku, Rika Fujimaru, Ryojiro Tanaka, Yuko Shima, Jiwon Baek, Hee Gyung Kang, Il-Soo Ha, Kyoung Hee Han, Eun Mi Yang, Asiri Abeyagunawardena, Brandon Lane, Megan Chryst-Stangl, Christopher Esezobor, Adaobi Solarin, Claire Dossier, Georges Deschênes, Marina Vivarelli, Hanna Debiec, Kenji Ishikura, Masafumi Matsuo, Kandai Nozu, Pierre Ronco, Hae Il Cheong, Matthew G Sampson, Katsushi Tokunaga, Kazumoto Iijima
    To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (Pmeta=6.71E-28, OR=1.88) and TNFSF15 (Pmeta=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).
    Nov. 2020, Kidney international, 98(5) (5), 1308 - 1322, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Takayuki Okamoto, Nana Sakakibara, Kandai Nozu, Toshiyuki Takahashi, Asako Hayashi, Yasuyuki Sato, China Nagano, Masafumi Matsuo, Kazumoto Iijima, Atsushi Manabe
    BACKGROUND: Approximately 15% of patients with Dent disease have pathogenic variants in the OCRL gene on Xq25-26, a condition that is referred to as Dent disease 2 (Dent-2). Dent-2 patients sometimes show mild extrarenal features of Lowe syndrome, such as mild mental retardation, suggesting that Dent-2 represents a mild form of Lowe syndrome. To date, eight female patients with Lowe syndrome have been reported, but no female Dent-2 patients have been reported. METHODS: In this study, we performed genetic testing of the first female Dent-2 patient to detect the presence of an OCRL variant. Aberrant splicing was demonstrated by in vivo, in vitro, and in silico assays, and skewed X-chromosome inactivation (XCI) in our patient and asymptomatic mothers of three Lowe patients with the heterozygous OCRL variant was evaluated by HUMARA assays using genomic DNA and RNA expression analysis. RESULTS: Our patient had an OCRL heterozygous intronic variant of c.1603-3G > C in intron 15 that led to a 169-bp insertion in exon 16, yielding the truncating mutation r.1602_1603ins (169) (p.Val535Glyfs*6) in exon 16. HUMARA assays of leukocytes obtained from this patient demonstrated incompletely skewed XCI (not extremely skewed). On the other hand, the asymptomatic mothers of 3 Lowe patients demonstrated random XCI. These results may lead to our patient's Dent-2 phenotype. CONCLUSIONS: This is the first report of a female patient clinically and genetically diagnosed with Dent-2 caused by an OCRL heterozygous splicing site variant and skewed XCI. Skewed XCI may be one of the factors associated with phenotypic diversity in female patients with Lowe syndrome and Dent-2.
    Oct. 2020, Clinical and experimental nephrology, 24(10) (10), 946 - 954, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Tomoko Horinouchi, Tomohiko Yamamura, China Nagano, Nana Sakakibara, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Koichi Nakanishi, Yuko Shima, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in COL4A3 or COL4A4, but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the COL4A3 and COL4A4 heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome. METHODS: We retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes. RESULTS: The median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality-causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (P<0.001). CONCLUSIONS: This study was the first to demonstrate the clinical importance in ARAS of focusing on variants in COL4A3 or COL4A4 that cause urinary abnormalities in both the homozygous or heterozygous state. Although heterozygous mutation carriers of COL4A3 and COL4A4 comprise a broad clinical spectrum, clinical information regarding each variant is important for predicting ARAS prognosis.
    Sep. 2020, Kidney360, 1(9) (9), 936 - 942, English, International magazine
    Scientific journal

  • Masahiro Nishiyama, Hiroshi Yamaguchi, Yusuke Ishida, Kazumi Tomioka, Hiroki Takeda, Noriyuki Nishimura, Kandai Nozu, Hiroki Mishina, Kazumoto Iijima, Hiroaki Nagase
    OBJECTIVE: To investigate the prevalence of seizures/febrile seizures in children up to 3 years of age and examine the effects of gestational age at birth on the risk for febrile seizures. DESIGN: Retrospective longitudinal population-based cohort study. SETTING: Kobe City public health center, Kobe, Japan, from 2010 to 2018. PARTICIPANTS: Children who underwent a medical check-up at 3 years of age. METHODS: Information regarding seizures was collected from the parents of 96 014 children. We identified the occurrence of seizure/febrile seizure in 74 017 children, whose gestational ages at birth were noted. We conducted a multivariate analysis with the parameter, gestational age at birth, to analyse the risk of seizure. We also stratified the samples by sex and birth weight (<2500 g or not) and compared the prevalence of seizure between those with the term and late preterm births. RESULTS: The prevalence of seizure was 12.1% (11.8%-12.3%), 13.2% (12.2%-14.4%), 14.6% (12.4%-17.7%) and 15.7% (10.5%-22.8%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. The prevalence of febrile seizures was 9.0% (8.8%-9.2%), 10.5% (9.5%-11.5%), 11.8% (9.7%-14.5%) and 11.2% (6.9%-17.7%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. Male was an independent risk factor for seizures (OR: 1.15, 95% CI 1.09 to 1.20; absolute risk increase 0.014, 95% CI 0.010 to 0.019) and febrile seizures (OR: 1.21, 95% CI 1.15 to 1.28; absolute risk increase 0.016, 95% CI 0.012 to 0.020), respectively. Late preterm birth was not associated with an increased risk of seizure/febrile seizure. CONCLUSIONS: Although very preterm birth may increase the risk of seizure/febrile seizure, the risk associated with late preterm birth is considerably small and less than that associated with male.
    Sep. 2020, BMJ open, 10(9) (9), e035977, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 詳細な腎病理観察がきっかけとなりIgA腎症と鑑別しえたX連鎖型Alport症候群の1例
    戸矢 智之, 濱野 直人, 中川 洋佑, 小泉 賢洋, 小倉 豪, 和田 健彦, 石河 慎也, 野津 寛大, 深川 雅史
    (一社)日本腎臓学会, Sep. 2020, 日本腎臓学会誌, 62(6) (6), 555 - 555, Japanese

  • Kentaro Nishi, Koichi Kamei, Masao Ogura, Mai Sato, Miki Murakoshi, Chikako Kamae, Ryutaro Suzuki, Toru Kanamori, China Nagano, Kandai Nozu, Kenji Ishikura, Shuichi Ito
    Denys-Drash syndrome is characterized by progressive nephropathy, gonadal dysgenesis, and Wilms tumor caused by a WT1 gene mutation. Infants with Denys-Drash syndrome frequently experience severe hypertension, but detailed clinical manifestations have yet to be clarified. Cases of infantile-onset Denys-Drash syndrome with severe hypertension at our hospital were retrospectively analyzed and the pathogenesis of hypertension was investigated. Six infants who received the diagnosis of Denys-Drash syndrome at the median age of 10 days (range: 2-182 days) were enrolled. Five infants had the complication of severe hypertension within a few days of diagnosis. All the patients showed rapid progression to end-stage renal disease and urgently required dialysis due to anuria/oliguria and hypervolemia with a median duration of 7.5 days (range: 0-17 days) on the day after diagnosis. Even under dialysis, all the patients continued to need antihypertensive treatment. Five patients underwent a preventive nephrectomy for Wilms tumor, and one patient underwent a nephrectomy due to progression to Wilms tumor. Two patients developed hypotension after a nephrectomy. The main causes of hypertension were hypervolemia in the predialysis stage, renin-associated hypertension in the dialysis stage, and multiple factors, including increased plasma catecholamine-associated hypertension in the postnephrectomy dialysis stage. At last the follow-up after bilateral nephrectomy, four of the five patients required antihypertensive treatment. Not all the patients showed target organ complications caused by hypertension. Severe hypertension is a common complication of infantile-onset Denys-Drash syndrome. The possibility of hypotension after nephrectomy should be considered in patients with Denys-Drash syndrome.
    Sep. 2020, The Tohoku journal of experimental medicine, 252(1) (1), 45 - 51, English, Domestic magazine
    Scientific journal

  • Daisuke Matsuoka, Shunsuke Noda, Motoko Kamiya, Yoshihiko Hidaka, Hisashi Shimojo, Yasushi Yamada, Tsutomu Miyamoto, Kandai Nozu, Kazumoto Iijima, Hiroyasu Tsukaguchi
    BACKGROUND: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive histology of immune-complex-type glomerulonephritis has been reported. However, the clinical relevance and etiologic mechanisms remain unknown. CASE PRESENTATION: A 5-year-old child presented with steroid-resistant nephrotic range proteinuria. Initial renal biopsy revealed predominant diffuse mesangial proliferation with a double-contour and coexisting milder changes of focal segmental glomerulosclerosis. Immunofluorescence and electron microscopy revealed a full-house-pattern deposition of immune complexes in the subendothelial and paramesangial areas. Serial biopsies at 6 and 8 years of age revealed that more remarkable changes of focal segmental glomerulosclerosis had developed on top of the initial proliferative glomerulonephritis. Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. CONCLUSIONS: Our findings, together with those of others, point to the importance of heterogeneity in clinicopathological phenotypes caused by Wilms tumor 1 mutations and suggest that immune-complex-mediated membranoproliferative glomerulopathy should be considered as a histological variant.
    Aug. 2020, BMC nephrology, 21(1) (1), 362 - 362, English, International magazine
    Scientific journal

  • Shinya Ishiko, Tomoko Horinouchi, Rika Fujimaru, Yuko Shima, Hiroshi Kaito, Ryojiro Tanaka, Shingo Ishimori, Atsushi Kondo, Sadayuki Nagai, Yuya Aoto, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Momoka Yoshimura, Koichi Nakanishi, Junya Fujimura, Naohiro Kamiyoshi, Hiroaki Nagase, Norishige Yoshikawa, Kazumoto Iijima, Kandai Nozu
    Galactose-deficient IgA1 (Gd-IgA1) is important in the pathogenesis of IgA nephropathy (IgAN). A Gd-IgA1-specific monoclonal antibody (KM55) has revealed glomerular Gd-IgA1 deposition solely in patients with IgAN and IgA vasculitis with nephritis (IgAV-N). However, this specificity is controversial and has not been demonstrated in pediatric patients. Here, we conducted double-immunofluorescence staining of IgA and Gd-IgA1 in 60 pediatric patients with various glomerular diseases. We divided patients into four groups: (1) patients with IgAN and IgAV-N (n = 23); (2) patients with immunocomplex-mediated glomerulonephritis accompanied by IgA deposition, including lupus nephritis, membranoproliferative glomerulonephritis, and membranous nephropathy (n = 14); (3) patients with other glomerular diseases involving IgA deposition, including idiopathic nephrotic syndrome (INS), oligomeganephronia, Alport syndrome, dense deposit disease, and crescentic glomerulonephritis (n = 11); and (4) patients with IgA-negative diseases including INS, membranoproliferative glomerulonephritis, membranous nephropathy, oligomeganephronia, Alport syndrome, C3 glomerulonephritis, poststreptococcal acute glomerulonephritis, and hemolytic uremic syndrome (n = 12). KM55 staining revealed Gd-IgA1-positive findings in 23/23 patients in Group 1 and 13/14 patients in Group 2, but not in patients in Groups 3 or 4. Therefore, KM55 may detect incidental IgA deposition in pediatric patients. Gd-IgA1 may be involved in the pathogenesis of these immune-related diseases; alternatively, KM55 may recognize IgA-related immunocomplexes in a non-specific manner.
    Aug. 2020, Scientific reports, 10(1) (1), 14026 - 14026, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoko Horinouchi, Tomohiko Yamamura, Shogo Minamikawa, China Nagano, Nana Sakakibara, Koichi Nakanishi, Yuko Shima, Naoya Morisada, Shinya Ishiko, Yuya Aoto, Hiroaki Nagase, Hiroki Takeda, Rini Rossanti, Shingo Ishimori, Hiroshi Kaito, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive, hereditary glomerular nephritis of variable severity caused by pathogenic COL4A5 variants. Currently, genetic testing is widely used for diagnosing XLAS; however, determining the pathogenicity of variants detected by such analyses can be difficult. Intronic variants or synonymous variants may cause inherited diseases by inducing aberrant splicing. Transcript analysis is necessary to confirm the pathogenicity of such variants, but it is sometimes difficult to extract mRNA directly from patient specimens. METHODS: In this study, we conducted in vitro splicing analysis using a hybrid minigene assay and specimens from three XLAS patients with synonymous variants causing aberrant splicing, including previously reported pathogenic mutations in the same codon. The variants were c.876 A>T (p.Gly292=), c.2358 A>G (p.Pro786=), and c.3906 A>G (p.Gln1302=). RESULTS: The results from our hybrid minigene assay were sufficient to predict splicing abnormalities; c.876 A>T cause 17-bp del and 35-bp del, c.2358 A>G cause exon 29 skipping, c.3906 A>G cause exon 42 skipping, which are very likely to cause pathogenicity. Further, patients carrying c.2358 A>G exhibited a mild phenotype that may have been associated with the presence of both normal and abnormally spliced transcripts. CONCLUSION: The minigene system was shown to be a sensitive assay and a useful tool for investigating the pathogenicity of synonymous variants.
    Aug. 2020, Molecular genetics & genomic medicine, 8(8) (8), e1342, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yusuke Ishida, Masahiro Nishiyama, Hiroshi Yamaguchi, Kazumi Tomioka, Tsukasa Tanaka, Hiroki Takeda, Shoichi Tokumoto, Daisaku Toyoshima, Azusa Maruyama, Yusuke Seino, Kazunori Aoki, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Kazumoto Iijima, Hiroaki Nagase
    PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.
    Aug. 2020, Seizure, 80, 12 - 17, English, International magazine
    [Refereed]
    Scientific journal

  • Alport症候群患者に対するエクソンスキッピング(ES)療法の開発
    野津 寛大, 山村 智彦, 堀之内 智子, 足立 朝美, 寺川 真紀, 高石 巨澄, 小泉 誠, 飯島 一誠
    (一社)日本腎臓学会, Jul. 2020, 日本腎臓学会誌, 62(4) (4), 362 - 362, Japanese

  • 小児における糖鎖不全IgA1免疫染色
    石河 慎也, 野津 寛大, 永井 貞之, 青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 石森 真吾, 貝藤 裕史, 田中 亮二郎, 飯島 一誠
    (一社)日本腎臓学会, Jul. 2020, 日本腎臓学会誌, 62(4) (4), 255 - 255, Japanese

  • スプライシング異常が疑われるCLCN5遺伝子変異のDent病発症メカニズムの解明
    井上 友彦, 長野 智那, 山村 智彦, 榊原 菜々, 堀之内 智子, 青砥 悠哉, 石河 慎也, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Jul. 2020, 日本腎臓学会誌, 62(4) (4), 257 - 257, Japanese

  • WT1遺伝子exon8-9ミスセンス変異における遺伝子型-臨床型の相関に関する検討
    長野 智那, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本腎臓学会, Jul. 2020, 日本腎臓学会誌, 62(4) (4), 293 - 293, Japanese

  • Lowe症候群とDent disease-2の2疾患における分子生物学的発症機序の解明
    榊原 菜々, 野津 寛大, 永井 貞之, 青砥 悠哉, 石河 慎也, 長野 智那, 堀之内 智子, 飯島 一誠
    (一社)日本腎臓学会, Jul. 2020, 日本腎臓学会誌, 62(4) (4), 293 - 293, Japanese

  • 森下 俊真, 渡邊 佳孝, 遠藤 翔太, 宮野 洋希, 梅田 千里, 西野 智彦, 仲川 真由, 村上 仁彦, 藤永 周一郎, 長野 智那, 野津 寛大, 飯島 一誠
    6歳男児。3歳児検尿で初めて尿蛋白(定性1+)を指摘されたが二次検尿で陰性だった。毎年の幼稚園検尿で尿蛋白陽性だったが経過観察された。胃腸炎罹患時、前医で高度蛋白尿を指摘され当院紹介となった。尿蛋白/Cre比(UP/UC)1.68と高度蛋白尿を認めたがネフローゼ症候群や腎機能障害はなく腎形態も正常だった。腎生検にて巣状分節性糸球体硬化症(focal segmental glomerulosclerosis:FSGS)のperihilar variantと診断した。遺伝子解析にてTRPC6(transient receptor potential cation channel 6)遺伝子にヘテロ接合体遺伝子変異c.523C>T(p.Arg175Trp)が同定され両親に変異は同定されずde novo変異と考えられた。レニンアンジオテンシン系阻害薬を開始しUP/UC1未満で改善傾向である。TRPC6遺伝子異常によるFSGSは成人期の診断が多いが自験例と同様の遺伝子異常を持つ過去の報告例は小児期発症だったと報告されている。ネフローゼ症候群を呈さない無症候性蛋白尿の小児で組織像がFSGSの場合、家族歴がなくてもネフローゼ症候群を呈する前に遺伝子解析を行うべきである。(著者抄録)
    日本小児腎不全学会, Jul. 2020, 日本小児腎不全学会雑誌, 40, 261 - 264, Japanese

  • Tomohiko Inoue, China Nagano, Masafumi Matsuo, Tomohiko Yamamura, Nana Sakakibara, Tomoko Horinouchi, Yugo Shibagaki, Daisuke Ichikawa, Yuya Aoto, Shinya Ishiko, Shingo Ishimori, Rini Rossanti, Kazumoto Iijima, Kandai Nozu
    BACKGROUND: In recent years, the elucidation of splicing abnormalities as a cause of hereditary diseases has progressed. However, there are no comprehensive reports of suspected splicing variants in the CLCN5 gene in Dent disease cases. We reproduced gene mutations by mutagenesis, inserted the mutated genes into minigene vectors, and investigated the pathogenicity and onset mechanisms of these variants. METHODS: We conducted functional splicing assays using a hybrid minigene for six suspected splicing variants (c.105G>A, c.105+5G>C, c.106-17T>G, c.393+4A>G, c.517-8A>G, c.517-3C>A) in CLCN5. We extracted information on these variants from the Human Gene Mutation Database. We reproduced minigene vectors with the insertion of relevant exons with suspected splicing variants. We then transfected these minigene vectors into cultured cells and extracted and analyzed the mRNA. In addition, we conducted in silico analysis to confirm our minigene assay results. RESULTS: We successfully determined that five of these six variants are pathogenic via the production of splicing abnormalities. One showed only normal transcript production and was thus suspected of not being pathogenic (c.106-17T>G). CONCLUSION: We found that five CLCN5 variants disrupted the original splice site, resulting in aberrant splicing. It is sometimes difficult to obtain mRNA from patient samples because of the fragility of mRNA or its low expression level in peripheral leukocytes. Our in vitro system can be used as an alternative to in vivo assays to determine the pathogenicity of suspected splicing variants.
    Jul. 2020, Clinical and experimental nephrology, 24(7) (7), 606 - 612, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomohiko Yamamura, Tomoko Horinouchi, Tomomi Adachi, Maki Terakawa, Yutaka Takaoka, Kohei Omachi, Minoru Takasato, Kiyosumi Takaishi, Takao Shoji, Yoshiyuki Onishi, Yoshito Kanazawa, Makoto Koizumi, Yasuko Tomono, Aki Sugano, Akemi Shono, Shogo Minamikawa, China Nagano, Nana Sakakibara, Shinya Ishiko, Yuya Aoto, Misato Kamura, Yutaka Harita, Kenichiro Miura, Shoichiro Kanda, Naoya Morisada, Rini Rossanti, Ming Juan Ye, Yoshimi Nozu, Masafumi Matsuo, Hirofumi Kai, Kazumoto Iijima, Kandai Nozu
    Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. We show that exon skipping enabled trimer formation, leading to remarkable clinical and pathological improvements including expression of the α5 chain on glomerular and the tubular basement membrane. In addition, the survival period was clearly prolonged in the ASO treated mice group. This data suggests that exon skipping may represent a promising therapeutic approach for treating severe male XLAS cases.
    Jun. 2020, Nature communications, 11(1) (1), 2777 - 2777, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • アルドステロン高値により診断に至った早産児の偽性低アルドステロン症1型の1例
    角谷 哲基, 牟禮 岳男, 河野 一誠, 武田 紗季, 住吉 倫卓, 榎本 真由子, 藤坂 方葉, 水野 洋介, 下村 真由美, 西野 昌光, 野津 寛大, 飯島 一誠, 吉井 勝彦
    (公社)日本小児科学会, Jun. 2020, 日本小児科学会雑誌, 124(6) (6), 1044 - 1044, Japanese

  • Yuko Shima, Koichi Nakanishi, Taketsugu Hama, Hironobu Mukaiyama, Masashi Sato, Yu Tanaka, Ryojiro Tanaka, Hiroshi Kaito, Kandai Nozu, Mayumi Sako, Kazumoto Iijima, Norishige Yoshikawa
    OBJECTIVES: Crescentic IgA nephropathy (C-IgAN) is defined as IgAN with more than 50% of glomeruli showing crescents. C-IgAN in children is rare; we investigate in detail for the first time. METHODS: We retrospectively analyzed the 515 consecutive children who were newly diagnosed with biopsy-proven IgAN between June 1976 and May 2010. We compared clinical and pathological findings between C-IgAN and non-C-IgAN. RESULTS: Among 515 cases of childhood IgAN, 25 children (4.9%) had C-IgAN. Of these 25, 16 children (64%) were referred to hospitals by annual school screening. Clinical findings showed significant differences in gross hematuria (76 vs. 50%, p = .03), excretion of proteinuria (1.9 vs. 0.5 g/day/m2, p < .0001), eGFR (102 vs. 108 ml/min/1.73 m2, p = .03), and duration from onset to renal biopsy (4.0 vs. 8.0 months, p = .04) between groups. Pathological findings showed significant differences in M1 (88 vs. 55%, p = .02), E1 (83 vs. 53%, p = .008), and presence of tubular atrophy/interstitial fibrosis (88 vs. 53%, p < .0001) between groups. The 16 children with C-IgAN were treated with prednisolone and immunosuppressant. Four cases (16%) reached chronic renal failure (eGFR < 60) at the latest observation (mean observation period: 6.0 ± 3.6 years). Patients with C-IgAN had significantly lower renal survival curve than non-C-IgAN patients according to Kaplan-Meier analysis (77.1% vs. 92.6% at 13 years, p < .0001). Compared with previous reports, however, they had better renal outcome. CONCLUSIONS: We confirmed the importance of school screening to find C-IgAN. Although most crescents (mean: 98.1%) of C-IgAN were cellular/fibrocellular, and acute lesions were well modified with combination therapy, the presence of tubular atrophy in C-IgAN may be the reason for poorer prognosis.
    Jun. 2020, Pediatric nephrology (Berlin, Germany), 35(6) (6), 1005 - 1014, English, International magazine
    Scientific journal

  • 母児間輸血症候群後に慢性腎臓病(CKD)に至った3例
    青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 藤岡 一路, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Jun. 2020, 日本小児科学会雑誌, 124(6) (6), 1036 - 1036, Japanese

  • 小児期に腎低形成と診断された新生児高β2ミクログロブリン尿症の1例
    永井 貞之, 仲宗根 瑠花, 菅 秀太郎, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 藤岡 一路, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Jun. 2020, 日本小児科学会雑誌, 124(6) (6), 1044 - 1044, Japanese

  • Rini Rossanti, Naoya Morisada, Kandai Nozu, Koichi Kamei, Tomoko Horinouchi, Tomohiko Yamamura, Shogo Minamikawa, Junya Fujimura, China Nagano, Nana Sakakibara, Takeshi Ninchoji, Hiroshi Kaito, Shuichi Ito, Ryojiro Tanaka, Kazumoto Iijima
    Pathogenic variants of paired box gene 2 (PAX2) cause autosomal-dominant PAX2-related disorder, which includes renal coloboma syndrome (RCS). Patients with PAX2-related disorder present with renal and ophthalmological pathologies, as well as with other abnormalities, including developmental problems and hearing loss. We sequenced PAX2 in 457 patients with congenital anomalies of the kidney and urinary tract or with renal dysfunction of unknown cause and identified 19 different pathogenic variants in 38 patients from 30 families (6.5%). Thirty-four patients had renal hypodysplasia or chronic kidney disease of unknown cause, and three had focal segmental glomerulosclerosis. Although no obvious genotype-phenotype correlation was observed, six of the seven patients who developed end-stage renal disease in childhood had truncating variants. Twenty-three patients had ocular disabilities, mostly optic disc coloboma. Non-renal and non-ophthalmological manifestations included developmental disorder, electrolyte abnormality, and gonadal abnormalities. Two unrelated patients had congenital cystic adenomatoid malformations in their lungs. Six of ten probands with PAX2 mutation identified by next-generation sequencing did not show typical RCS manifestations. We conclude that PAX2-related disorder has a variable clinical presentation and can be diagnosed by next-generation sequencing even in the absence of typical RCS manifestations.
    Jun. 2020, Journal of human genetics, 65(6) (6), 541 - 549, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Misato Kamura, Tomohiko Yamamura, Kohei Omachi, Mary Ann Suico, Kandai Nozu, Shota Kaseda, Jun Kuwazuru, Tsuyoshi Shuto, Kazumoto Iijima, Hirofumi Kai
    Introduction: Alport syndrome is a hereditary glomerulonephritis that results from the disruption of collagen α345(IV) heterotrimerization caused by mutation in COL4A3, COL4A4 or COL4A5 genes. Many clinical studies have elucidated the correlation between genotype and phenotype, but there is still much ambiguity and insufficiency. Here, we focused on the α345(IV) heterotrimerization of α5(IV) missense mutant as a novel factor to further understand the pathophysiology of Alport syndrome. Methods: We selected 9 α5(IV) missense mutants with typical glycine substitutions that clinically differed in disease progression. To quantify the trimerization of each mutant, split nanoluciferase-fused α3/α5 mutants and α4 were transfected into the cells, and intracellular and secreted heterotrimer were detected by luminescence using an assay that we developed previously. Results: Trimer formation and secretion patterns tended to be similar to the wild type in most of the mutations that did not show proteinuria at a young age. On the other hand, trimer secretion was significantly reduced in all the mutations that showed proteinuria and early onset of renal failure. One of these mutants has low ability of intracellular trimer formation, and the others had the defect of low-level secretion. In addition, the mutant that is assumed to be nonpathogenic has similar trimer formation and secretion pattern as wild-type α5(IV). Conclusion: The result of cell-based α345(IV) heterotrimer formation assay was largely correlated with clinical genotype-phenotype. These trimerization assessments provide additional phenotypic considerations and may help to distinguish between pathogenic and nonpathogenic mutations.
    May 2020, Kidney international reports, 5(5) (5), 718 - 726, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kei Nishiyama, Mari Kurokawa, Michiko Torio, Yasunari Sakai, Mitsuru Arima, Shoko Tsukamoto, Satoshi Obata, Shogo Minamikawa, Kandai Nozu, Noriyuki Kaku, Yoshihiko Maehara, Koh-Hei Sonoda, Tomoaki Taguchi, Shouichi Ohga
    BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have extended the lifespan of patients, whereas the full clinical spectrum of PS in infancy and beyond remains elusive. CASE PRESENTATION: We present the case of a 12-month-old boy with PS, manifesting as the bilateral microcoria and congenital nephrotic syndrome. He was born without asphyxia, and was neurologically intact from birth through the neonatal period. Generalized muscle weakness and hypotonia were recognized from 3 months of age. The infant showed recurrent vomiting at age 5 months of age, and was diagnosed with gastroesophageal reflux and intestinal malrotation. Despite the successful surgical treatment, vomiting persisted and led to severely impaired growth. Tulobuterol treatment was effective in reducing the frequency of vomiting. Targeted sequencing confirmed that he had a compound heterozygous mutation in LAMB2 (NM_002292.3: p.Arg550X and p.Glu1507X). A search of the relevant literature identified 19 patients with severe neuro-muscular phenotypes. Among these, only 8 survived the first 12 months of life, and one had feeding difficulty with similar gastrointestinal problems. CONCLUSIONS: This report demonstrated that severe neurological deficits and gastrointestinal dysfunction may emerge in PS patients after the first few months of life.
    Apr. 2020, BMC medical genetics, 21(1) (1), 80 - 80, English, International magazine
    Scientific journal

  • Hiroshi Yamaguchi, Masahiro Nishiyama, Shoichi Tokumoto, Yusuke Ishida, Kazumi Tomioka, Kazunori Aoki, Yusuke Seino, Daisaku Toyoshima, Hiroki Takeda, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima, Hiroaki Nagase
    OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome characterized by biphasic seizures with impaired consciousness. AESD is rare outside Asia, and consecutive cohort studies are therefore scarce. Herein, we aimed to describe the detailed characteristics of AESD, including clinical course, electroencephalogram data, laboratory data, imaging findings, treatment, and outcomes. METHODS: We reviewed the clinical database and medical charts of 43 consecutive pediatric patients (<18 years old) who developed AESD between October 1, 2002, and September 30, 2019. RESULTS: We found that AESD occurred even though patients did not develop prolonged seizures. A comparison between the two groups (first seizure duration <30 min and first seizure duration ≥30 min) revealed three main findings: first, patients with AESD who had shorter seizures had better prognosis than those with prolonged seizures; second, patients with AESD who had shorter seizures tended to have earlier occurrence of a second seizure; and third, high signal intensity on diffusion-weighted magnetic resonance imaging was observed mainly in frontal areas, not diffusely, in patients with shorter seizures, and in a broader area in patients with prolonged seizures. CONCLUSIONS: Our description of the detailed clinical picture of AESD may add new insight into its pathophysiology.
    Apr. 2020, Journal of the neurological sciences, 411, 116684 - 116684, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Naoya Morisada, Riku Hamada, Kenichiro Miura, Ming Juan Ye, Kandai Nozu, Motoshi Hattori, Kazumoto Iijima
    Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by retinitis pigmentosa (RP), truncal obesity, cognitive impairment, hypogonadism in men, polydactyly, and renal abnormalities with severe renal dysfunction. Twenty-two causative genes have already been reported for this disorder. In this study, we identified two unrelated Japanese patients with clinical diagnoses of BBS associated with compound heterozygous SCLT1 mutation. Patient 1 was a 10-year-old girl, and patient 2 was a 22-year-old man. Both the patients showed severe renal dysfunction in childhood, RP, mild intellectual disability, short stature, and truncal obesity, without oral aberrations and polydactyly. Patient 2 also had hypogonadism. We identified two missense variants in SCLT1, c.[1218G > A] and [1631A > G], in both the patients by next-generation sequencing. Subsequent cDNA analysis revealed that c.1218G > A affected exon 14 skipping in SCLT1. To date, SCLT1 has been reported as the causative gene of oral-facial-digital syndrome type IX, and Senior-Løken syndrome. The phenotypes of both the present patients were compatible with BBS. These results highlight SCLT1 as an additional candidate for BBS phenotype in an autosomal recessive manner.
    Apr. 2020, CEN case reports, English, Domestic magazine
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • Satoshi Hibino, Naoya Morisada, Asami Takeda, Kazuki Tanaka, Kandai Nozu, Satoshi Yamakawa, Kazumoto Iijima, Naoya Fujita
    Mutations in the TTC21B gene have been identified in patients with nephronophthisis and were recently found in some patients with focal segmental glomerulosclerosis. We herein report a Japanese boy with end-stage renal disease due to medullary polycystic kidney disease and primary focal segmental glomerulosclerosis. Next-generation sequencing detected a new compound heterozygous missense mutation in the TTC21B gene. His renal pathological findings and gene mutations have not been previously reported in patients with ciliopathy. For children with severe renal dysfunction, mutations in the TTC21B gene cause both ciliopathy characterized by bilateral polycystic kidney disease and primary focal segmental glomerulosclerosis.
    Apr. 2020, Internal medicine (Tokyo, Japan), English, Domestic magazine
    [Refereed]

  • WT1遺伝子異常症
    長野 智那, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 野津 寛大, 飯島 一誠
    WT1遺伝子はWilms腫瘍の原因遺伝子として単離された遺伝子である。WT1蛋白はC末端に4つのZnフィンガー構造(DNA結合ドメイン)を有し、DNA上の転写調節配列に結合し転写因子として働く。腎臓の発生過程に発現し分化調節に働き、生後も糸球体上皮細胞に発現してポトサイトの構造維持に関与している。WT1遺伝子異常症は常染色体優性遺伝形式を呈し、変異の部位により多彩な症状を呈する事が特徴である。乳児期に発症する進行性の腎障害、Wilms腫瘍、性分化異常を呈するDenys-Drash症候群患者の大部分はDNA結合ドメインをコードするエクソン8あるいは9のミスセンス変異が存在する。その結果生じる異常なWT1蛋白は、Dominant negative効果により正常WT1蛋白の機能を低下させるため重症になると考えられている。ここではWT1遺伝子の機能と疾患について簡単に説明する。(著者抄録)
    発達腎研究会, Apr. 2020, 発達腎研究会誌, 28(1) (1), 29 - 32, Japanese

  • 齊藤 綾子, 泉 維昌, 鈴木 竜太郎, 塚越 隆司, 林 立申, 塩野 淳子, 堀米 仁志, 稲垣 隆介, 濱田 陸, 幡谷 浩史, 緒方 謙太郎, 森貞 直哉, 野津 寛大, 飯島 一誠, 須磨崎 亮
    頭蓋外胚葉異形成(cranioectodermal dysplasia:CED)は頭蓋,顔面,骨格の形成異常,ネフロン癆を呈する慢性腎臓病を特徴とした常染色体劣性遺伝疾患でSensenbrenner症候群とも呼ばれる.我々はWDR35複合ヘテロ接合性変異を有するCEDの姉妹例を経験した.症例1(姉),症例2(妹)ともに頭蓋骨縫合早期癒合症の手術歴があった.症例1は3歳時に顔色不良で受診し,急性心不全,腎不全を認めた.症例2は症例1の診断を契機に1歳9か月時に腎臓外来を受診した.症例1,2ともに腎病理組織はネフロン癆に矛盾せず,腎代替療法を導入した.過去の血液検査では乳児期から腎機能障害を認めていたが指摘されず,慢性腎臓病の進行とともに循環器合併症が認められた.頭蓋・顔面・骨格の形成異常を伴う場合CEDを念頭に腎機能を確認し,診断・管理を行うことは合併症を防ぐうえで重要である.(著者抄録)
    (一社)日本小児腎臓病学会, Apr. 2020, 日本小児腎臓病学会雑誌, 33(1) (1), 43 - 50, Japanese

  • Ichiro Morioka, Yasumasa Kakei, Takashi Omori, Kandai Nozu, Kazumichi Fujioka, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Yoshinori Ito, Akira Oka
    BACKGROUND: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. METHODS: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age ≥32 weeks at birth and weighing ≥1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. DISCUSSION: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.
    Apr. 2020, Medicine, 99(17) (17), e19765, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Shogo Minamikawa, Saori Miwa, Tetsuji Inagaki, Kei Nishiyama, Hiroshi Kaito, Takeshi Ninchoji, Tomohiko Yamamura, China Nagano, Nana Sakakibara, Shingo Ishimori, Shigeo Hara, Norishige Yoshikawa, Daishi Hirano, Ryoko Harada, Riku Hamada, Natsuki Matsunoshita, Michio Nagata, Yuko Shima, Koichi Nakanishi, Hiroaki Nagase, Hiroki Takeda, Naoya Morisada, Kazumoto Iijima, Kandai Nozu
    Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin β2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin β2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.
    Apr. 2020, Journal of human genetics, 65(4) (4), 355 - 362, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kandai Nozu, Tomohiko Yamamura, Tomoko Horinouchi, China Nagano, Nana Sakakibara, Kenji Ishikura, Riku Hamada, Naoya Morisada, Kazumoto Iijima
    Bartter syndrome (BS) and Gitelman syndrome (GS) are syndromes associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis. Clinically, BS is classified into two types: the severe antenatal/neonatal type, which develops during the fetal period with polyhydramnios and preterm delivery; and the relatively mild classic type, which is usually found during infancy with failure to thrive. GS can be clinically differentiated from BS by its age at onset, usually after school age, or laboratory findings of hypomagnesemia and hypocalciuria. Recent advances in molecular biology have shown that these diseases can be genetically classified into type 1 to 5 BS and GS. As a result, it has become clear that the clinical classification of antenatal/neonatal BS, classic BS, and GS does not always correspond to the clinical symptoms associated with the genotypes in a one-to-one manner; and there is clinically no clear differential border between type 3 BS and GS. This has caused confusion among clinicians in the diagnosis of these diseases. It has been proposed that the disease name "inherited salt-losing tubulopathy" can be used for cases of tubulopathies accompanied by hypokalemia and metabolic alkalosis. It is reasonable to use this term prior to genetic typing into type 1-5 BS or GS, to avoid confusion in a clinical setting. In this article, we review causative genes and phenotypic correlations, diagnosis, and treatment strategies for salt-losing tubulopathy as well as the clinical characteristics of pseudo-BS/GS, which can also be called a "salt-losing disorder".
    Apr. 2020, Pediatrics international : official journal of the Japan Pediatric Society, 62(4) (4), 428 - 437, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Oligomeganephronia9例の臨床病理学的検討
    兵頭 俊紀, 西 愼一, 吉川 徳茂, 野津 寛大, 飯島 一誠, 原 重雄, 伊藤 智雄
    (一社)日本病理学会, Mar. 2020, 日本病理学会会誌, 109(1) (1), 437 - 437, Japanese

  • X染色体連鎖型Alport症候群患者におけるサイレント変異の病的意義の検討
    堀之内 智子, 野津 寛大, 近藤 淳, 永井 貞之, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 山村 智彦, 森貞 直哉, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 237 - 237, Japanese

  • Dent disease-1とDent disease-2の臨床像の差異に関する検討
    榊原 菜々, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 長野 智那, 堀之内 智子, 山村 智彦, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 238 - 238, Japanese

  • 日本人における遺伝性ネフローゼ症候群の網羅的遺伝子診断体制
    長野 智那, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 305 - 305, Japanese

  • 糖鎖不全IgA1免疫染色が診断に有用であったステロイド抵抗性ネフローゼ症候群の1例
    石河 慎也, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 305 - 305, Japanese

  • Yuki Kyono, Kandai Nozu, Taku Nakagawa, Yuichi Takami, Hideki Fujita, Tomoaki Ioroi, Masaaki Kugo, Kazumoto Iijima, Naohiro Kamiyoshi
    Renal tubular acidosis (RTA) is a rare disease caused by a defect of urinary acidification. The ammonium chloride loading test is the gold standard method for determining the type of RTA. However, because this test has some side effects (e.g., nausea, vomiting, and stomach discomfort), applying this test for pediatric cases is difficult. Recently, a loading test with the combination of furosemide and fludrocortisone was reported to be an alternative to the ammonium chloride loading test, with 100% sensitivity and specificity in adult's cases. We report the first pediatric case of distal RTA in a patient who was successfully diagnosed by a drug loading test with the combination of furosemide and fludrocortisone without any side effects. We also performed genetic analysis and detected a known pathogenic variant in the SLC4A1 gene. The combination loading test of furosemide and fludrocortisone is a useful and safe diagnostic tool for pediatric cases of RTA.
    NLM (Medline), Feb. 2020, CEN case reports, 9(1) (1), 81 - 86, English
    Scientific journal

  • 小児IgA腎症の組織学的軽症例と重症例における多剤併用療法の効果に関する比較
    青砥 悠哉, 野津 寛大, 近藤 淳, 石河 慎也, 榊原 菜々, 長野 智那, 藤村 順也, 堀之内 智子, 山村 智彦, 神吉 直宙, 石森 真吾, 島 友子, 中西 浩一, 吉川 徳茂, 貝藤 裕史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 303 - 303, Japanese

  • アルカリ化療法開始後,精神発達の伸びを認めた近位尿細管性アシドーシスの1例
    八木 麻理子, 粟野 宏之, 野津 寛大, 森貞 直哉, 河崎 洋子, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 421 - 421, Japanese

  • 2度の腎生検で診断に至らなかったX染色体連鎖型Alport症候群の一女児例
    藤井 裕子, 松村 英樹, 白数 明彦, 中倉 兵庫, 山崎 哲司, 野津 寛大, 飯島 一誠, 芦田 明
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 417 - 417, Japanese

  • NICU退院児における感覚特性,発達障害特性の検討
    村尾 真理子, 前山 花織, 万代 ツルエ, 堀之内 智子, 冨岡 和美, 福嶋 祥代, 阿部 真也, 大山 正平, 藤岡 一路, 野津 寛大, 飯島 一誠, 高木 康子, 加藤 威, 岡田 由香, 溝渕 雅巳, 北山 真次, 永瀬 裕朗, 森岡 一郎, 高田 哲, 西村 範行
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 271 - 271, Japanese

  • 症候性先天性サイトメガロウイルス感染症を対象とした抗ウイルス薬治療の医師主導治験
    森岡 一朗, 伊藤 嘉規, 森内 浩幸, 吉川 哲史, 藤岡 一路, 野津 寛大, 岡 明
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 378 - 378, Japanese

  • 小児期に腎低形成と診断された新生児高β2ミクログロブリン尿症の1例
    永井 貞之, 西田 浩輔, 藤岡 一路, 南川 将吾, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 418 - 418, Japanese

  • 2度の腎生検で診断に至らなかったX染色体連鎖型Alport症候群の一女児例
    藤井 裕子, 松村 英樹, 白数 明彦, 中倉 兵庫, 山崎 哲司, 野津 寛大, 飯島 一誠, 芦田 明
    (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 417 - 417, Japanese

  • Ken Saida, Koichi Kamei, Naoya Morisada, Masao Ogura, Kentaro Ogata, Kentaro Matsuoka, Kandai Nozu, Kazumoto Iijima, Shuichi Ito
    Springer Science and Business Media LLC, Feb. 2020, CEN Case Reports, 9(1) (1), 19 - 23
    [Refereed]
    Scientific journal

  • China Nagano, Tomohiko Yamamura, Tomoko Horinouchi, Yuya Aoto, Shinya Ishiko, Nana Sakakibara, Yuko Shima, Koichi Nakanishi, Hiroaki Nagase, Kazumoto Iijima, Kandai Nozu
    Numerous disease-causing gene mutations have been identified in proteinuric diseases, such as nephrotic syndrome and glomerulosclerosis. This report describes the results of comprehensive genetic diagnosis of Japanese patients with severe proteinuria. In addition, the report describes the clinical characteristics of patients with monogenic disease-causing mutations. We conducted comprehensive gene screening of patients who had either congenital nephrotic syndrome, infantile nephrotic syndrome, steroid-resistant nephrotic syndrome, or focal segmental glomerular sclerosis. Using targeted next-generation sequencing, 60 podocyte-related genes were screened in 230 unrelated patients with proteinuria. A retrospective review of clinical data was conducted for these patients. We detected monogenic disease-causing mutations in 30% (69 of 230) of patients among 19 of the screened genes. Common genes with disease-causing mutations were WT1 (25%), NPHS1 (12%), INF2 (12%), TRPC6 (10%), and LAMB2 (9%). With various immunosuppressive or renoprotective therapies, remission of proteinuria in patients with unknown causative mutations was observed in 26% of patients, whereas only 5% of patients with monogenic disease-causing mutations exhibited complete remission. We assessed the genetic backgrounds of Japanese patients with severe proteinuria. The proportion of patients with gene defects was similar to that of other reports, but the disease-causing gene mutation frequency was considerably different.
    Jan. 2020, Scientific reports, 10(1) (1), 270 - 270, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ayumi Shishido, Naoya Morisada, Kenta Tominaga, Hiroyasu Uemura, Akiko Haruna, Hiroaki Hanafusa, Kandai Nozu, Kazumoto Iijima
    NAA10-related syndrome is an extremely rare X-chromosomal disorder, the symptoms of which include intellectual disability (ID), ocular anomalies, or congenital heart diseases, such as hypertrophic cardiomyopathy (HCM). Here, we describe a 4-year-old Japanese male patient who exhibited mild ID, HCM, and specific facial features. A hemizygous mutation (NM_003491.3: c.455_458del, p. Thr152Argfs*6) in exon 7 of NAA10 was detected. We recommend that patients undergo precise medical follow-up considering the characteristics of NAA10-related syndrome.
    2020, Human genome variation, 7, 23 - 23, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomomi Aizawa, Naoya Morisada, Kandai Nozu, Satoru Tandai, Hiroshi Tanaka
    Wiley, Jan. 2020, Pediatrics International, 62(1) (1), 101 - 103
    [Refereed]
    Scientific journal

  • Takeshi Goda, Hiroshi Komatsu, Kandai Nozu, Hisakazu Nakajima
    2020, Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 29(3) (3), 127 - 130, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Koichi Kamei, Kenji Ishikura, Mayumi Sako, Shuichi Ito, Kandai Nozu, Kazumoto Iijima
    Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.
    Jan. 2020, Pediatric nephrology (Berlin, Germany), 35(1) (1), 17 - 24, English, International magazine
    [Refereed]
    Scientific journal

  • Takeshi Oba, Shunsuke Kobayashi, Yuko Nakamura, Mototsugu Nagao, Kandai Nozu, Izumi Fukuda, Kazumoto Iijima, Hitoshi Sugihara
    A 21-year-old man presented with hyperthyroidism and hypokalemia and was treated for thyrotoxic hypokalemic periodic paralysis caused by Graves' disease. Thyroid function soon normalized but hypokalemia persisted. Laboratory data revealed hyperreninemic hyperaldosteronism and metabolic alkalosis consistent with Gitelman Syndrome. The patient was found to have a previously unreported compound heterozygous mutation of T180K and L858H in the SLC12A3 gene, and Gitelman Syndrome was diagnosed. He was started on eplerenone to control serum potassium level. Alternative diagnoses should be considered when electrolyte imbalances persist after disease resolution.
    Dec. 2019, Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 86(5) (5), 301 - 306, English, Domestic magazine
    Scientific journal

  • 市川 裕太, 藤岡 一路, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠
    症例は在胎34週0日、二絨毛膜二羊膜双胎の第2子の女児で、仮死なく出生した。出生体重2000g、Apgarスコア7点/9点であった。多呼吸、陥没呼吸が持続し、早産、低出生体重、呼吸障害のため入院となった。呼気吸気変換方式気道陽圧法で呼吸管理、定型的管理を開始した。入院後初回の血液検査にて、高マグネシウム血症を認めたがナトリウム(Na)、カリウム(K)値は正常であった。精査のため提出した検査で、血中アルドステロン濃度5310pg/mL、レニン活性34.8ng/mL/時であり、低Na高K血症とあわせて偽性低アルドステロン症と診断した。出生直後の一過性にアルドステロン不応性を呈し、以降は無治療で自然軽快した経緯から、本症例は二次性にI型偽性低アルドステロン症の病態を呈するIII型(続発性)偽性低アルドステロン症と診断した。また、出生後同じく早産、低出生体重、呼吸障害のために入院となっていた第1子の男児については、血中アルドステロン濃度4720pg/mL、レニン活性>45ng/mL/時と高値を認めた。
    (株)東京医学社, Dec. 2019, 周産期医学, 49(12) (12), 1675 - 1678, Japanese

  • 堀之内 智子, 野津 寛大, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 南川 将吾, 山村 智彦, 貝藤 裕史, 森貞 直哉, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2019, 日本小児腎臓病学会雑誌, 32(2) (2), 139 - 139, Japanese

  • 治療法の再整理とアップデートのために 専門家による私の治療 バーター(Bartter)症候群
    野津 寛大, 飯島 一誠
    (株)日本医事新報社, Nov. 2019, 日本医事新報, (4984) (4984), 36 - 36, Japanese
    [Refereed]

  • 治療法の再整理とアップデートのために 専門家による私の治療 ギッテルマン(Gitelman)症候群
    野津 寛大, 飯島 一誠
    (株)日本医事新報社, Nov. 2019, 日本医事新報, (4984) (4984), 37 - 37, Japanese
    [Refereed]

  • 【小児の救急・搬送医療】病態と疾患 腎尿路系 ネフローゼ症候群
    南川 将吾, 野津 寛大, 飯島 一誠
    (株)東京医学社, Nov. 2019, 小児内科, 51(増刊) (増刊), 644 - 647, Japanese
    [Refereed]

  • X染色体連鎖型Alport症候群におけるsplicing異常の同定と臨床遺伝学的検討
    堀之内 智子, 野津 寛大, 飯島 一誠
    X染色体連鎖型Alport症候群(XLAS)患者に対してトランスクリプト解析を行い、splicing異常により発症していた男性患者ではそのトランスクリプトレベルでtruncatingかnon-truncatingかを区別し、遺伝子型と臨床像の相関関係を比較した。当科で遺伝学的に診断を行った279家系のXLASのうち、71家系(25%)はtruncating変異、159家系(57%)はnon-truncating変異、49家系(18%)はsplicing異常をきたしており、splicing異常の41家系を検討対象とした。Human Splicing Finderを用いたin silico解析の結果から、19家系では完全にsplicingパターンを予測可能であり、17家系ではsplicing異常の可能性は予測できるものの、実際のsplicingパターンは予測不能であり、5家系ではsplicing異常の可能性が予測不能であった。29家系46例の男性患者の腎生存曲線を作成し求めたESRDに至った年齢の中央値はnon-truncating群で29歳、truncating群で20歳であり、統計学的有意差をもってnon-truncating群で腎予後が良好であった。
    (一社)日本腎臓学会, Nov. 2019, 日本腎臓学会誌, 61(8) (8), 1136 - 1138, Japanese
    [Refereed]

  • Takashi Iijima, Noriko Hayami, Kenmei Takaichi, Naoya Morisada, Kandai Nozu, Kazumoto Iijima, Naoki Sawa, Junichi Hoshino, Yoshifumi Ubara
    Orofaciodigital syndrome 1 (OFD-1) is a rare, X-linked, dominantly inherited disorder caused by an OFD1 mutation that can cause polycystic kidneys. A 37-year-old woman on hemodialysis therapy was admitted to our hospital for trans-catheter arterial embolization therapy for enlarged polycystic kidneys. Lobulated tongue and brachydactyly were noticed, prompting an OFD1 sequencing analysis. Sequencing revealed a causal four-base-pair deletion in exon 13, both in the patient and in her mother, whose renal function had been retained. The peripheral leukocyte X chromosome inactivation pattern was skewed in the patient but not in her mother, suggesting some role in their phenotypic difference.
    Oct. 2019, Internal medicine (Tokyo, Japan), 58(20) (20), 2989 - 2992, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Takeshi Oba, Shunsuke Kobayashi, Yuko Nakamura, Mototsugu Nagao, Kandai Nozu, Izumi Fukuda, Kazumoto Iijima, Hitoshi Sugihara
    A 21-year-old man presented with hyperthyroidism and hypokalemia and was treated for thyrotoxic hypokalemic periodic paralysis caused by Graves' disease. Thyroid function soon normalized but hypokalemia persisted. Laboratory data revealed hyperreninemic hyperaldosteronism and metabolic alkalosis consistent with Gitelman Syndrome. The patient was found to have a previously unreported compound heterozygous mutation of T180K and L858H in the SLC12A3 gene, and Gitelman Syndrome was diagnosed. He was started on eplerenone to control serum potassium level. Alternative diagnoses should be considered when electrolyte imbalances persist after disease resolution.
    MEDICAL ASSOC NIPPON MEDICAL SCH, Oct. 2019, JOURNAL OF NIPPON MEDICAL SCHOOL, 86(5) (5), 301 - 306, English
    Scientific journal

  • 【腎生検から病因と病態を読む】病理診断で遺伝子検査を依頼されたら?
    榊原 菜々, 野津 寛大, 森貞 直哉, 飯島 一誠
    (株)東京医学社, Oct. 2019, 腎と透析, 87(4) (4), 660 - 663, Japanese
    [Refereed]

  • 【嚢胞性腎疾患】ネフロン癆の最近の知見
    森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Oct. 2019, 日本腎臓学会誌, 61(7) (7), 1102 - 1107, Japanese
    [Refereed]

  • Tomoko Horinouchi, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, China Nagano, Nana Sakakibara, Koichi Nakanishi, Yuko Shima, Naoya Morisada, Shinya Ishiko, Yuya Aoto, Hiroaki Nagase, Hiroki Takeda, Rini Rossanti, Hiroshi Kaito, Masafumi Matsuo, Kazumoto Iijima
    X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5. In XLAS cases suspected of being caused by aberrant splicing, transcript analysis needs to be conducted to determine splicing patterns and assess the pathogenicity. However, such analysis is not always available. We conducted a functional splicing assay using a hybrid minigene for seven COL4A5 intronic mutations: one was identified by us and six were found in the Human Gene Mutation Database. The minigene assay revealed exon skipping in four variants, exon skipping and a 10-bp insertion in one variant, and no change in one variant, which appeared not to be pathogenic. For one variant, our assay did not work. The results of all three cases for which transcript data were available were consistent with our assay results. Our findings may help to increase the accuracy of genetic test results and clarify the mechanisms causing aberrant splicing.
    Sep. 2019, Scientific reports, 9(1) (1), 12696 - 12696, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshitaka Watanabe, Shuichiro Fujinaga, Koji Sakuraya, Naoya Morisada, Kandai Nozu, Kazumoto Iijima
    Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is characterized by primary ciliary dysfunction (ciliopathy) and progresses to end-stage kidney disease (ESKD) during the second decade of life (juvenile and adolescent NPHP) or before the age of 3 years (infantile NPHP). Here we describe the case of an infant with NPHP who carries a homozygous mutation in SDCCAG8 (also called NPHP10 or BBS16) that encodes SDCCAG8 (serologically defined colon cancer antigen 8). SDCCAG8 is localized at the centrioles of both renal epithelial cells and retinal photoreceptor cells. A mutation in SDCCAG8 is also associated with Bardet-Biedl syndrome (BBS), characterized by NPHP, obesity, polydactyly, and rod-cone dystrophy. A 2-year-old boy was referred to our hospital due to kidney dysfunction of unknown etiology; the patient presented with delayed development and opsoclonus but did not exhibit the clinical characteristics of BBS. Histological findings such as dilatation of tubules and irregular thickness of tubular basement membrane confirmed the diagnosis of NPHP. Four months after referral, the patient's renal function was rapidly deteriorated, and emergency peritoneal dialysis was initiated. Next-generation sequencing (NGS) was performed, showing that the patient carries a homozygous four-base-pair deletion in SDCCAG8 (c.849_852delTTTG, p.Cys283Ter). The patient's parents were also found to be heterozygous for this loss-of-function mutation. To the best of our knowledge, the present patient is the first case of biopsy-proven infantile NPHP with a homozygous SDCCAG8 mutation. We conclude that NGS is extremely useful in the identification of SDCCAG8-related NPHP as a cause of sudden-onset ESKD during infancy.
    Sep. 2019, The Tohoku journal of experimental medicine, 249(1) (1), 29 - 32, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Kazumi Tomioka, Masahiro Nishiyama, Hiroaki Nagase, Yusuke Ishida, Tsukasa Tanaka, Shoichi Tokumoto, Hiroshi Yamaguchi, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Kazunori Aoki, Yusuke Seino, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Kazumoto Iijima
    OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.
    Sep. 2019, Brain & development, 41(8) (8), 691 - 698, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • China Nagano, Naoya Morisada, Kandai Nozu, Koichi Kamei, Ryojiro Tanaka, Shoichiro Kanda, Shinichi Shiona, Yoshinori Araki, Shinichiro Ohara, Chieko Matsumura, Katsuaki Kasahara, Yukiko Mori, Akane Seo, Kenichiro Miura, Miki Washiyama, Keisuke Sugimoto, Ryoko Harada, Satoshi Tazoe, Hiroyo Kourakata, Mayumi Enseki, Daisuke Aotani, Takeshi Yamada, Nana Sakakibara, Tomohiko Yamamura, Shogo Minamikawa, Kenji Ishikura, Shuichi Ito, Motoshi Hattori, Kazumoto Iijima
    BACKGROUND: Hepatocyte nuclear factor 1β (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. METHODS: We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. RESULTS: Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m2; p = 0.0091). CONCLUSION: We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.
    Sep. 2019, Clinical and experimental nephrology, 23(9) (9), 1119 - 1129, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomohiko Yamamura, Kandai Nozu, Shogo Minamikawa, Tomoko Horinouchi, Nana Sakakibara, China Nagano, Yuya Aoto, Shinya Ishiko, Koichi Nakanishi, Yuko Shima, Hiroaki Nagase, Rini Rossanti, Ming J Ye, Yoshimi Nozu, Shingo Ishimori, Naoya Morisada, Hiroshi Kaito, Kazumoto Iijima
    BACKGROUND: Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3-5 genes. Recently, comprehensive genetic analysis has become the first-line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published. METHODS: In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next-generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group). RESULTS: In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%. DISCUSSION: Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathogenic mutations missed by Sanger sequencing.
    Sep. 2019, Molecular genetics & genomic medicine, 7(9) (9), e883, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 急速に末期腎不全に至りSDCCAG8遺伝子異常が同定されたネフロン癆関連ciliopathyの2歳男児
    渡邊 佳孝, 藤永 周一郎, 遠藤 翔太, 梅田 千里, 西野 智彦, 仲川 真由, 村上 仁彦, 森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Aug. 2019, 日本腎臓学会誌, 61(6) (6), 740 - 740, Japanese

  • WT-1遺伝子exon7に新規ミスセンス変異が同定されたステロイド抵抗性ネフローゼ症候群の12歳女児
    宮野 洋希, 藤永 周一郎, 遠藤 翔太, 西野 智彦, 梅田 千里, 渡邊 佳孝, 仲川 真由, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Aug. 2019, 日本腎臓学会誌, 61(6) (6), 746 - 746, Japanese

  • 生後3ヵ月時発症のステロイド感受性ネフローゼ症候群の一例
    梅田 千里, 藤永 周一郎, 長野 智那, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Aug. 2019, 日本腎臓学会誌, 61(6) (6), 747 - 747, Japanese

  • IV型コラーゲンα5鎖染色正常巣状分節性糸球体硬化症で遺伝子診断にてAlport症候群と診断した1例
    大多尾 早紀, 河野 圭志, 吉川 美喜子, 後藤 俊介, 藤井 秀毅, 野津 寛大, 西 慎一
    (一社)日本腎臓学会, Aug. 2019, 日本腎臓学会誌, 61(6) (6), 883 - 883, Japanese

  • Kentaro Nishi, Tomohiro Inoguchi, Koichi Kamei, Riku Hamada, Hiroshi Hataya, Masao Ogura, Mai Sato, Takako Yoshioka, Kentaro Ogata, Shuichi Ito, Koichi Nakanishi, Kandai Nozu, Yuko Hamasaki, Kenji Ishikura
    BACKGROUND: Neonatal-onset Denys-Drash syndrome (NODDS) is a distinctive clinical entity and has a poor renal and life outcome. Early diagnosis of NODDS is important for managing disorders of sexual development and determining assigned gender. Although patients with NODDS and congenital nephrotic syndrome of the Finnish type (CNF) present with nephrotic syndrome in neonatal life or infancy, the clinical course of NODDS and factors distinguishing these diseases at onset is unknown. METHODS: We performed a retrospective cohort study of patients with NODDS and CNF between 1997 and 2017. Patients with nephrotic syndrome and WT1 or NPHS1 mutations with neonatal onset (within 30 days) were eligible. RESULTS: We studied eight patients with NODDS and 15 with CNF. The median serum creatinine level at onset in the NODDS group was significantly higher (1.85 mg/dL) than that in the CNF group (0.15 mg/dL; P = 0.002). The median placental/fetal weight ratio in the NODDS and CNF group was 41.8% and 21.0%, respectively (P = 0.001). Kaplan-Meier analysis showed that the median number of days for progression to ESRD from onset in the NODDS and CNF groups was 6 and 910 days, respectively (P < 0.001). All patients in the NODDS group were alive at follow-up. Only one patient in the CNF group died of cardiac complications during follow-up. CONCLUSION: CNS, renal dysfunction at onset, and a relatively large placenta are prominent signs of NODDS. Prognosis for patients with NODDS is satisfactory if appropriate and active management is performed.
    Aug. 2019, Clinical and experimental nephrology, 23(8) (8), 1058 - 1065, English, Domestic magazine
    [Refereed]
    Scientific journal

  • 医学と医療の最前線 腎疾患の遺伝子診断と遺伝子標的療法
    野津 寛大
    (一社)日本内科学会, Aug. 2019, 日本内科学会雑誌, 108(8) (8), 1598 - 1606, Japanese
    [Refereed]

  • Sho Ishiwa, Mai Sato, Naoya Morisada, Kentaro Nishi, Toru Kanamori, Mika Okutsu, Masao Ogura, Mayumi Sako, Motomichi Kosuga, Koichi Kamei, Shuichi Ito, Kandai Nozu, Kazumoto Iijima, Kenji Ishikura
    BACKGROUND: The association between the clinical presentation of congenital anomalies of the kidney and urinary tract (CAKUT) and gene mutations has yet to be fully explored. METHODS: In this retrospective cohort study, we examined patients with CAKUT who underwent gene analysis. The analysis was performed in patients with bilateral renal lesions, extrarenal complications, or a family history of renal disease. The data from the diagnosis, gene mutations, and other complications were analyzed. RESULTS: In total, 66 patients with CAKUT were included. Of these, gene mutations were detected in 14 patients. Bilateral renal lesions were significantly related to the identification of gene mutations (p = 0.02), and no gene mutations were observed in patients with lower urinary tract obstruction (six patients). There was no significant difference in the rate of gene mutations between those with or without extrarenal complications (p = 0.76). The HNF1β gene mutation was identified in most of the patients with hypodysplastic kidney with multicystic dysplastic kidney (six of seven patients). There was no significant difference in the presence or absence of gene mutations with respect to the renal survival rate (log-rank test p = 0.53). The renal prognosis varied, but the differences were not statistically significant for any of the gene mutations. CONCLUSIONS: CAKUT with bilateral renal lesions were significantly related to gene mutations. We recommend that CAKUT-related gene analysis be considered in cases of bilateral renal lesions. No gene mutations were observed in patients with lower urinary tract obstruction. The renal prognosis varied for each gene mutation.
    Aug. 2019, Pediatric nephrology (Berlin, Germany), 34(8) (8), 1457 - 1464, English, International magazine
    [Refereed]
    Scientific journal

  • Tsukasa Tanaka, Hiroaki Nagase, Hiroshi Yamaguchi, Yusuke Ishida, Kazumi Tomioka, Masahiro Nishiyama, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Kandai Nozu, Noriyuki Nishimura, Hiroshi Kurosawa, Ryojiro Tanaka, Kazumoto Iijima
    BACKGROUND: Seizures and/or impaired consciousness accompanied by fever without known etiology (SICF) is common in the pediatric emergency setting. No optimal strategy for the management of SICF in childhood currently exists. We previously demonstrated the effectiveness of targeted temperature management (TTM) against SICF with a high risk of morbidity; however, some patients with SICF develop neurological sequelae despite TTM, which necessitate additional neuroprotective treatment. The clinical characteristics of these severe cases have not been studied. Accordingly, the aim of this study was to identify the clinical characteristics of children with SICF who exhibit poor outcomes after TTM. METHODS: The medical records of children admitted to Kobe Children's Hospital (Kobe, Japan) between October 2002 and September 2016 were retrospectively reviewed. Patients with SICF treated using TTM were included and divided into the satisfactory and poor outcome groups. Univariate and multivariate logistic regression analyses were used to compare clinical characteristics and laboratory findings between the two groups. RESULTS: Of the 73 included children, 10 exhibited poor outcomes. Univariate logistic regression analysis revealed that acute circulatory failure before TTM initiation, the use of four or more types of anticonvulsants, methylprednisolone pulse therapy, and an aspartate aminotransferase (AST) level ≥73 IU/L were associated with poor outcomes. Multivariate logistic regression analysis identified an elevated AST level as a significant independent predictor of a poor outcome. CONCLUSIONS: An elevated AST level within 12 h of onset in children with SICF is an independent predictor of a poor outcome after TTM initiated within 24 h of onset.
    Aug. 2019, Brain & development, 41(7) (7), 604 - 613, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nagano C, Sako M, Kamei K, Ishikura K, Nakamura H, Nakanishi K, Omori T, Nozu K, Iijima K
    BACKGROUND: Eighty percent of children with idiopathic nephrotic syndrome respond well to steroid therapy, but up to 50% of patients with steroid-sensitive nephrotic syndrome exhibit frequently relapsing (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Several studies identified the chimeric anti-CD20 monoclonal antibody rituximab as an effective treatment for patients with complicated FRNS/SDNS. Recent studies suggested that rituximab could also be a first-line treatment for early-stage uncomplicated FRNS/SDNS, although further studies are required to confirm its efficacy and safety. METHODS/DESIGN: We are conducting a multicenter, double-blind, randomized placebo controlled trial to investigate the efficacy and safety of rituximab for the treatment of childhood-onset early-stage uncomplicated FRNS/SDNS. Patients will be allocated to receive two 375 mg/m2 doses (maximum dose: 500 mg) of either rituximab or placebo. Investigators are permitted to request the disclosure of a subject's allocation code if he or she exhibits treatment failure. Additionally, if placebo-treated subjects display early relapse (a sign of treatment failure), they have the option to receive rituximab in an unblinded phase. The primary endpoint is relapse-free survival during the observation period. DISCUSSION: The results will provide important data on the use of rituximab for patients with uncomplicated FRNS/SDNS. In the future, rituximab treatment will enable most patients with uncomplicated FRNS/SDNS to discontinue or reduce steroid therapy without relapse, and it is possible that rituximab could represent an immunosuppressive therapy for these diseases. TRIAL REGISTRATION: This trial was prospectively registered to the JMACCT Clinical Trials Registry on September 6, 2018 (Trial ID: JMA-IIA00380 ).
    Aug. 2019, BMC nephrology, 20(1) (1), 293 - 293, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroyuki Hashimoto, Naro Ohashi, Naoko Tsuji, Yoshitaka Naito, Shinsuke Isobe, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Kandai Nozu, Kazumoto Iijima, Hideo Yasuda
    Background: Thin basement membrane nephropathy (TBMN) is a relatively common disease. Patients typically present with isolated hematuria, which has a good renal prognosis. In contrast, glomerulocystic kidney disease (GCKD) is a rare disease, associated with slow progressive renal dysfunction. To our knowledge, co-occurring diagnosis of TBMN with GCKD has not been reported previously. Case presentation: A 30-year old woman was admitted to our hospital for evaluation of hematuria and renal insufficiency. Upon examination, her urinary protein level was 40 mg/day and occult blood in her urine was 2+. The patient's urinary dysmorphic red blood cell sediment was 30-49/high power field. In contrast, her serum creatinine levels increased from 0.57 mg/dl to 0.86 mg/dl during the previous 2-years, without special events. She suffered from far-sightedness and astigmatism beginning at birth She had no family history of renal disease. Renal biopsy demonstrated cystic dilatation of the Bowman's capsule and atrophy of the glomerular tuft. The glomerular basement membrane (GBM) was thin, with an average thickness of 191 nm. Next-generation sequencing was used to evaluate for mutations in COL4A3 and COL4A4, associated with TBMN, and UMOD, MUC1, and SEC61A1, associated with hereditary GCKD. No pathogenic mutations were identified. We thus diagnosed the patient with TBMN coexistent with sporadic GCKD. Conclusion: We report the patient diagnosed with TBMN accompanied by sporadic GCKD, based on renal biopsy and genetic testing. Because it is possible that other diseases, such as GCKD, can coexist with TBMN, it is important to consider renal biopsy.
    BioMed Central Ltd., Jul. 2019, BMC Nephrology, 20(1) (1), English
    Scientific journal

  • 当科における24時間自由行動下血圧測定(ABPM)の使用経験
    榊原 菜々, 青砥 悠哉, 石河 慎也, 長野 智那, 南川 将吾, 山村 智彦, 野津 寛大, 飯島 一誠
    24時間自由行動下血圧測定(ABPM)は、白衣高血圧の診断や血圧の日内変動の確認に有用であるが、小児科領域においてはまだ一般的でないのが現状である。当科でABPMを行った小児もしくは小児期発症の腎疾患患者について検討した。ABPMにはフクダ電子デジタルホルタ記録器FM-800およびA&Dメディカル携帯型自動血圧計TM-243が使用された。また血圧測定は、日中は30分間隔、夜間就寝時は60分間隔で行われた。【症例1】14歳女児。肥満あり。扁桃切除の術前検査ではじめて高血圧を指摘された。Ca拮抗薬内服下でも高血圧が残存し、ABPMを施行したところDipper型の持続性高血圧と診断された。【症例2】18歳男性。早産児、極低出生体重児。学校検尿で蛋白尿を指摘され、精査受診時に高血圧と左腎萎縮を認めた。ABPMを施行したところ、血圧は正常であり、白衣高血圧と診断された。【症例3】14歳男児。頻回再発型ネフローゼ症候群のフォロー中、11歳ごろより高血圧を認めていた。当初ステロイド性と考えられていたが、ステロイド中止後もCa拮抗薬内服下で高血圧が持続し本態性高血圧と考えられていた。ABPMを施行したところ血圧は正常であった。白衣高血圧と考えられたため、降圧薬を減量・中止した。【症例4】13歳男児。学校検尿異常の精査目的で受診した際、高血圧を指摘された。家庭血圧でも高血圧があり、ABPMを施行したところ、覚醒時の高血圧を認めた。【症例5】26歳女性。ステロイド抵抗性ネフローゼ症候群のフォロー中、25歳頃より高血圧を認めていた。ABPMを施行したところDipper型の持続性高血圧と診断された。【症例6】29歳男性。ステロイド抵抗性ネフローゼ症候群による末期腎不全で腎移植後。受診時に高血圧を認め、ABPMを施行したところ、夜間高血圧(Non-dipper型)と診断された。【考察】小児におけるABPMの明確な適応基準は示されていないが、小児科領域においても、診察室血圧や家庭血圧のみでは高血圧の診断・管理は不十分であり、ABPMの積極的な使用が望ましい。(著者抄録)
    日本小児高血圧研究会, Jul. 2019, 日本小児高血圧研究会誌, 16(1) (1), 14 - 21, Japanese

  • Hiroshi Komatsu, Takeshi Goda, Kandai Nozu
    Alport syndrome (AS) is an inherited kidney disease that may lead to end-stage renal disease in early adult life. It is a clinically and genetically heterogeneous nephropathy. The possibility of a patient with haematuria or proteinuria being diagnosed as having AS cannot be excluded even if the patient is female or if the family history is unknown. We report a 3-year-old girl with a de novo frameshift mutation, c.3906delA p.(Gly1303Aspfs∗17), in the COL4A5 gene. The significance of the electron microscopic study on the glomerular basement membrane must be emphasised because it is the first step towards the diagnosis of AS. Genetic analysis provides the only conclusive diagnosis of AS, by determining the mode of inheritance and prognosis.
    BMJ Publishing Group, Jul. 2019, BMJ Case Reports, 12(7) (7), English
    Scientific journal

  • 腎石灰化、低Mg血症を契機に診断に至った遺伝性Mg喪失性腎症の一例
    出崎 緑, 稲葉 彩, 西山 邦幸, 坂本 正宗, 神垣 祐, 大杉 康司, 大山 宜孝, 東 聡美, 渡辺 好宏, 町田 裕之, 武下 草生子, 志賀 健太郎, 伊藤 秀一, 大谷 方子, 野津 寛大
    (公社)神奈川県医師会, Jul. 2019, 神奈川医学会雑誌, 46(2) (2), 228 - 228, Japanese

  • 無症候性蛋白尿の精査でWT1遺伝子異常が判明した17歳女児例
    金森 透, 亀井 宏一, 西 健太朗, 奥津 美夏, 石和 翔, 佐藤 舞, 小椋 雅夫, 伊藤 秀一, 中西 啓太, 野津 寛大, 飯島 一誠, 石倉 健司
    無症候性蛋白尿の精査の結果、WT1遺伝子関連腎症と診断された症例を経験したため報告する。症例は6歳時に学校検尿で軽度蛋白尿を認め、当院紹介となった。来院時高度蛋白尿のほかは異常所見なく、腎生検所見も微小変化群であり、無症候性蛋白尿として経過観察された。16歳時に軽度腎機能障害を認め遺伝子解析を行い、WT1遺伝子のIntron9に既報のヘテロ接合体変異を認めた。WT1遺伝子のIntron9の変異はステロイド抵抗性ネフローゼ症候群の精査で見つかることが多いが、一部には無症候性蛋白尿の精査で診断に至った報告もある。TRPC6やNUP107など他の遺伝子異常においても定期検尿を契機に無症候性蛋白尿の精査で発見されたとする報告がある。本症例では遺伝子検査で治療方針の確認や腎予後の予測などの臨床上のメリットが得られており、無症候性蛋白尿の症例においても高度蛋白尿が持続し、腎外病変の存在や腎機能障害の出現などの兆候がみられた場合、遺伝性腎疾患の可能性を考慮する必要があると考えた。(著者抄録)
    日本小児腎不全学会, Jul. 2019, 日本小児腎不全学会雑誌, 39, 207 - 210, Japanese
    [Refereed]

  • 櫻谷 浩志, 藤永 周一郎, 梅田 千里, 富井 祐治, 渡邊 佳孝, 野津 寛大, 森貞 直哉, 飯島 一誠
    【背景】PAX2遺伝子変異により腎コロボーマ症候群が発症するとされている。今回、腎病変のみを認めた新規PAX2遺伝子変異の女児例を経験した。【症例】児は胎生期異常指摘なく35週、1,864gで出生、腎機能障害のため生後3ヵ月時に当院紹介となった。家族歴として、母が尿蛋白を契機に17歳で原因不明の慢性腎不全と診断されている。当院初診時、顔貌異常や外表奇形はなく、腎機能障害(Cre 0.5mg/dL)、尿検査異常(尿TP/Cre 1.66g/gCr、尿β2MG 15,329μg/L)を認めた。超音波で両腎サイズ低下、DMSAで取り込み率低下(右5.9%、左7.2%)があり両側低形成腎と診断した。3歳時に遺伝子検査を依頼したところ、母児にPAX2遺伝子のヘテロ接合体の新規ミスセンス変異(c.70G>C、p.Gly24Arg)を認めた。後に眼科診察を行ったが母児ともに異常はなかった。【考察】PAX2遺伝子変異に腎外病変は必須ではなく、腎機能障害の家族歴を有する両側低形成腎の症例では遺伝子検査を検討してもよいと考えられた。(著者抄録)
    日本小児腎不全学会, Jul. 2019, 日本小児腎不全学会雑誌, 39, 108 - 110, Japanese
    [Refereed]

  • Shimizu M, Irabu H, Kaneda H, Ohta K, Nozu K
    Jul. 2019, Pediatrics international : official journal of the Japan Pediatric Society, 61(7) (7), 726 - 727, English, International magazine
    [Refereed]
    Scientific journal

  • Tomoko Horinouchi, Naoya Morisada, Hiroyasu Uemura, Daisuke Kobayashi, Kandai Nozu, Nobuhiko Okamoto, Kazumoto Iijima
    X-linked dominant chondrodysplasia punctata (Conradi-Hunermann-Happle syndrome, CDPX2) caused by mutations in the emopamil-binding protein (EBP) gene and congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome caused by mutation in the NAD(P)H steroid dehydrogenase-like (NSDHL) gene are rare, typically male lethal disorders. CDPX2 skin lesions are characterized by transient severe congenital ichthyosis following the lines of Blaschko, whereas in CHILD syndrome, the lesions show striking lateralization. Here, we report a male CDPX2 patient with postzygotic mosaicism of the EBP gene presenting with lateralized skin lesions with strict midline demarcation as seen in CHILD syndrome (although this diagnosis was ruled out based on analysis of NSDHL), but also partly distributed along Blaschko's lines as seen in CDPX2. The lesions resolved within a few months, but the patient had other abnormalities, including shortening of the limbs, epiphyseal stippling, and forearm asymmetry; he also had problems with respiration and feeding in the first 4 years after birth. Kyphoscoliosis with dysplastic vertebral bodies progressed rapidly and required posterior spinal fusion surgery at 6 years old. These findings provide insights into the pathophysiology of CDPX2 and the mechanism of asymmetric lesion formation during development.
    Jul. 2019, American journal of medical genetics. Part A, 179(7) (7), 1315 - 1318, English, International magazine
    [Refereed]

  • Rini Rossanti, Akemi Shono, Kenichiro Miura, Motoshi Hattori, Tomohiko Yamamura, Keita Nakanishi, Shogo Minamikawa, Junya Fujimura, Tomoko Horinouchi, China Nagano, Nana Sakakibara, Hiroshi Kaito, Hiroaki Nagase, Naoya Morisada, Katsuhiko Asanuma, Masafumi Matsuo, Kandai Nozu, Kazumoto Iijima
    Advances in molecular genetics have revealed that approximately 30% of cases with steroid-resistant nephrotic syndrome (SRNS) are caused by single-gene mutations. More than 50 genes are responsible for SRNS. One such gene is the nucleoporin, 93-KD (NUP93). Thus far, few studies have reported mutations of NUP93 in SRNS. Here, we describe an NUP93 biallelic mutation in a 9-year-old boy with focal segmental glomerular sclerosis (FSGS). Notably, one mutation comprised an intronic variant; we conducted in vivo and in vitro analysis to characterize this variant. We found two heterozygous mutations in NUP93: c.2137-18G>A in intron 19 and a novel nonsense mutation c.727A>T (p.Lys243*) in exon 8. We conducted RNA sequencing and in vitro splicing assays by using minigene construction, combined with protein expression analysis to determine the pathogenicity of the intronic variant. Both RNA sequencing and in vitro splicing assay showed exon 20-skipping by the intronic variant. In protein expression analysis, aberrant subcellular localization with small punctate vesicles in the cytoplasm was observed for the intronic variant. Taken together, we concluded that c.2137-18G>A was linked to pathogenicity due to aberrant splicing. NUP93 variants are quite rare; however, we have shown that even intronic variants in NUP93 can cause SRNS. This study provides a fundamental approach to validate the intronic variant, as well as new insights regarding the clinical spectrum of SRNS caused by rare gene variants.
    Jul. 2019, Journal of human genetics, 64(7) (7), 673 - 679, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 【指定難病ペディア 2019】個別の指定難病 腎・泌尿器系 アルポート症候群[指定難病218]
    野津 寛大, 飯島 一誠
    (公社)日本医師会, Jun. 2019, 日本医師会雑誌, 148(特別1) (特別1), S249 - S249, Japanese
    [Refereed]

  • Masahiro Nishiyama, Hiroaki Nagase, Kazumi Tomioka, Tsukasa Tanaka, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Kyoko Fujita, Azusa Maruyama, Kaori Sasaki, Yoshinobu Oyazato, Taku Nakagawa, Yuichi Takami, Kandai Nozu, Noriyuki Nishimura, Ichiro Nakashima, Kazumoto Iijima
    The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ± 3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ± 3.7 days, 6.0 ± 4.5 days, and 26 ± 34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ± 4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.
    Jun. 2019, Brain & development, 41(6) (6), 531 - 537, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yuko Shima, Koichi Nakanishi, Mayumi Sako, Mari Saito-Oba, Yuko Hamasaki, Hiroshi Hataya, Masataka Honda, Koichi Kamei, Kenji Ishikura, Shuichi Ito, Hiroshi Kaito, Ryojiro Tanaka, Kandai Nozu, Hidefumi Nakamura, Yasuo Ohashi, Kazumoto Iijima, Norishige Yoshikawa
    BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .
    May 2019, Pediatric nephrology (Berlin, Germany), 34(5) (5), 837 - 846, English, International magazine
    [Refereed]
    Scientific journal

  • NPHS1は小児ステロイド感受性ネフローゼ症候群の疾患感受性遺伝子である
    山村 智彦, 長野 智那, 堀之内 智子, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 298 - 298, Japanese

  • 常染色体劣性Alport症候群39家系46人の臨床遺伝学的検討
    堀之内 智子, 野津 寛大, 榊原 菜々, 長野 智那, 南川 将吾, 山村 智彦, 飯島 一誠
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 318 - 318, Japanese

  • 石森 真吾, 堀之内 智子, 藤村 順也, 南川 将吾, 山村 智彦, 松野下 夏樹, 神吉 直宙, 小椋 雅夫, 貝藤 裕史, 野津 寛大, 亀井 宏一, 石倉 健司, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 100 - 100, Japanese

  • 遺伝性ネフローゼ症候群における臨床的特徴の検討
    長野 智那, 野津 寛大, 青砥 悠哉, 石河 慎也, 榊原 菜々, 南川 将吾, 山村 智彦, 飯島 一誠
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 303 - 303, Japanese

  • Dent病およびLowe症候群の臨床遺伝学的検討
    榊原 菜々, 野津 寛大, 青砥 悠哉, 石河 慎也, 長野 智那, 南川 将吾, 山村 智彦, 飯島 一誠
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 355 - 355, Japanese

  • 長野 智那, 野津 寛大, 青砥 悠哉, 石河 慎也, 榊原 菜々, 南川 将吾, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 91 - 91, Japanese

  • 堀之内 智子, 野津 寛大, 石河 慎也, 青砥 悠哉, 榊原 菜々, 長野 智那, 南川 将吾, 山村 智彦, 貝藤 裕史, 森貞 直哉, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 92 - 92, Japanese

  • 榊原 菜々, 野津 寛大, 青砥 悠哉, 石河 慎也, 長野 智那, 南川 将吾, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 180 - 180, Japanese

  • 小児IgA腎症における蛋白尿再燃因子の検討
    島 友子, 中西 浩一, 浜 武継, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 342 - 342, Japanese

  • 和田 卓三, 島 友子, 濱 武継, 田中 侑, 向山 弘展, 佐藤 匡, 鈴木 啓之, 吉川 徳茂, 中西 浩一, 野津 寛大, 飯島 一誠, 澤井 俊宏
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 104 - 104, Japanese

  • 石河 慎也, 野津 寛大, 青砥 悠哉, 榊原 菜々, 長野 智那, 南川 将吾, 山村 智彦, 島 友子, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 119 - 119, Japanese

  • 青砥 悠哉, 野津 寛大, 石河 慎也, 榊原 菜々, 長野 智那, 藤村 順也, 南川 将吾, 山村 智彦, 神吉 直宙, 石森 真吾, 島 友子, 中西 浩一, 吉川 徳茂, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 120 - 120, Japanese

  • ミトコンドリア病関連腎疾患の全国調査
    今澤 俊之, 野津 寛大, 北村 博司, 服部 元史
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 267 - 267, Japanese

  • ADTKD-MUC1/UMODの抗体診断法確立へ向けた検討
    岡田 絵里, 森貞 直哉, 李 紀廉, 森 維久郎, 福田 亜純, 上原 正樹, 川口 武彦, 首村 守俊, 北村 博司, 野津 寛大, 飯島 一誠, 今澤 俊之
    (一社)日本腎臓学会, May 2019, 日本腎臓学会誌, 61(3) (3), 317 - 317, Japanese

  • 三輪 沙織, 山田 哲史, 川上 雄平, 徳永 愛, 武政 洋一, 梅田 千里, 掛川 大輔, 伊藤 亮, 長野 智那, 野津 寛大, 飯島 一誠, 平野 大志
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 179 - 179, Japanese

  • 松村 千恵子, 菅谷 雅人, 升田 真依, 小林 雅代, 鵜野 裕一, 金本 勝義, 北村 博司, 澤井 俊宏, 奥田 雄介, 才田 謙, 野津 寛大, 尾田 高志
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 106 - 106, Japanese

  • 飯島 一誠, Xiaoyuan Jia, 山村 智彦, 人見 祐基, 長野 智那, 堀之内 智子, 野津 寛大, 徳永 勝士
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 56 - 56, Japanese

  • Keita Nakanishi, Takayuki Okamoto, Kandai Nozu, Shigeo Hara, Yasuyuki Sato, Asako Hayashi, Toshiyuki Takahashi, China Nagano, Nana Sakakibara, Tomoko Horinouchi, Junya Fujimura, Shogo Minamikawa, Tomohiko Yamamura, Rini Rossanti, Hiroaki Nagase, Hiroshi Kaito, Tadashi Ariga, Kazumoto Iijima
    BACKGROUND: Recently, comprehensive genetic approaches for steroid-resistant nephrotic syndrome (SRNS) using next-generation sequencing (NGS) have been established, but causative gene mutations could not be detected in almost 70% of SRNS patients. Main reason for the low variant detection rate is that most of them are SRNS caused not by genetic but by immunological factors. But some of them are probably because of the difficulty of detecting copy number variations (CNVs) in causative genes by NGS. METHODS: In this study, we performed two analytical methods of NGS data-dependent pair analysis and custom array comparative genomic hybridization (aCGH) in addition to NGS analysis in an infantile nephrotic syndrome case. RESULTS: We detected only one known pathogenic heterozygous missense mutation in exon 7 of COQ6 c.782C > T, p.(Pro261Leu) by NGS. With pair analysis, heterozygous exon 1-2 deletion was suspected and was confirmed by custom aCGH. As a result, a small CNV was successfully detected in the COQ6 gene. Because we could detect variants in COQ6 and could start treatment by coenzyme Q10 (CoQ10) in his very early stage of SRNS, the patient achieved complete remission. CONCLUSIONS: These relatively novel methods should be adopted in cases with negative results in gene tests by NGS analysis. Especially, in cases with CoQ10 deficiency, it is possible to delay initiating dialysis by starting treatment at their early stages.
    May 2019, Clinical and experimental nephrology, 23(5) (5), 669 - 675, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 伊良部 仁, 清水 正樹, 井上 なつみ, 水田 麻雄, 谷内江 昭宏, 金田 尚, 太田 和秀, 野津 寛大
    (一社)日本小児腎臓病学会, Apr. 2019, 日本小児腎臓病学会雑誌, 32(1) (1), 54 - 55, Japanese

  • 佐藤 朋子, 浅野 貴子, 橋本 淳也, 山本 かずな, 山村 智彦, 野津 寛大, 飯島 一誠, 野々山 恵章
    Alport症候群は、IV型コラーゲンα鎖の異常により、進行性腎障害、感音性難聴、眼科的異常を来す遺伝性疾患である。病初期は顕微鏡的血尿が唯一の所見であるため、早期に診断することは困難とされる。今回我々は、3歳児検尿で血尿・蛋白尿を指摘され、7歳時の第1回腎生検で非IgAメサンギウム増殖性腎炎と暫定診断され、11歳時の第2回腎生検のIV型コラーゲン染色によりAlport症候群と診断した男児例を経験した。遺伝形式はIV型コラーゲンα5鎖の染色パターンからは常染色体劣性型が疑われたが、遺伝子解析でCOL4A5 exon21に9塩基の欠失によるインフレーム変異を認め、X染色体連鎖型と診断した。Alport症候群は、IV型コラーゲン染色や遺伝子解析で診断が可能であるため、持続性血尿の鑑別疾患として積極的に考慮する必要がある。(著者抄録)
    (一社)日本小児腎臓病学会, Apr. 2019, 日本小児腎臓病学会雑誌, 32(1) (1), 31 - 36, Japanese

  • 【小児の負荷試験2019】腎機能検査 アルドステロン症診断のための確認試験 カプトプリル負荷試験、フロセミド立位負荷試験、生理食塩水負荷試験
    野津 寛大
    ＜Key Points＞(1)原発性アルドステロン症は小児ではまれだが、常染色体優性の家族性アルドステロン症は小児期に発症する。(2)高血圧を呈する場合、必ず血漿アルドステロン/レニン比(ARR)を測定する。ARR200以上で本疾患を疑う。(3)3種類の負荷試験のうち、1種類以上陽性で確定診断となる。(著者抄録)
    (株)東京医学社, Apr. 2019, 小児内科, 51(4) (4), 563 - 564, Japanese
    [Refereed]

  • PAX2関連腎疾患の遺伝子型と臨床像
    森貞 直哉, Rossanti Rini, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠
    【緒言】PAX2は腎発生に重要な転写因子をコードする遺伝子で、10q24に位置する。PAX2は常染色体優性遺伝機序により腎コロボーマ症候群や先天性腎尿路異常、巣状糸球体硬化症の原因となることが報告されている。【方法】2010年から2018年までに神戸大学で遺伝子解析を行い、PAX2の異常を同定した患者について検討した。本研究は神戸大学倫理委員会での承認を受け行った。【結果】25家系34名でPAX2の遺伝子異常を同定した。変異のタイプはフレームシフト変異が最も多く14家系に認められた。患者の男女比は1:1であった。腎疾患としては腎低形成または原因不明の腎機能障害とされていた例が多かった。腎外合併症としては20症例で眼合併症が認められ、そのほかに自閉症や知的障害、先天性嚢胞性肺疾患、卵巣嚢胞などが認められた。解析手法として、次世代シークエンサー(NGS)での網羅的解析で同定した例が7家系あった。遺伝子型と表現型には明らかな相関関係は認めなかった。【考察】今回の検討ではpaired domainの短縮型変異が多かったが、スプライス部位や全欠失などほぼ全ての型が認められた。腎外症状としては14例では眼合併症は認められず、必須の症状ではなかった。非特異的な臨床症状を認めた場合、NGSでの網羅的解析は原因診断に有用であった。(著者抄録)
    発達腎研究会, Apr. 2019, 発達腎研究会誌, 27(1) (1), 31 - 34, Japanese
    [Refereed]

  • オリゴメガネフロニアと角膜ジストロフィ
    長野 智那, 青砥 悠哉, 石河 慎也, 榊原 菜々, 南川 将吾, 山村 智彦, 野津 寛大, 飯島 一誠
    オリゴメガネフロニアは腎低形成の一型ともいわれており、ネフロン数の減少と残存糸球体の代償性肥大を主な組織学的特徴とする。一方、角膜ジストロフィは遺伝性進行性角膜疾患である。両者は今まで完全に関連のない疾患と考えられていた。しかし近年、単一因子の遺伝性眼疾患の原因遺伝子が明らかになってきており、両者の合併症例が散見される。ここでは両疾患とその関連について簡単に説明する。(著者抄録)
    発達腎研究会, Apr. 2019, 発達腎研究会誌, 27(1) (1), 7 - 8, Japanese
    [Refereed]

  • 男性腎不全の家族歴からネフロン癆関連シリオパチーの診断に至った3歳男児例
    和田 卓三, 島 友子, 浜 武継, 向山 弘展, 鈴木 啓之, 森貞 直哉, 野津 寛大, 飯島 一誠, 中西 浩一
    一次繊毛とその関連構造物の遺伝子変異により発症する一群の疾患を称して繊毛病と呼ぶが、腎徴候を呈する繊毛病としては、多発性嚢胞腎、ネフロン癆やネフロン癆関連シリオパチー(nephronophthisis-related ciliopathy:NPHP-RC)と多岐にわたる。今回、男性腎徴候の家族歴の集積及び、遺伝学的診断の進歩からNPHP-RCの診断に至った家族例を経験した。症例は、3歳の男児。腹部エコーにて偶然両側の腎腫大、腎実質の輝度上昇を指摘された。腎機能の軽度低下を認め、家族歴で母方の兄弟に腎不全を認めることから、X連鎖遺伝によるNPHP-RCを疑い、遺伝子解析からOFD1遺伝子異常と診断した。児は現在、保存期腎不全であり、腎移植を含め経過観察としている。臨床症状と家族歴から疾患を疑い、遺伝子解析が診断に有用であった。(著者抄録)
    発達腎研究会, Apr. 2019, 発達腎研究会誌, 27(1) (1), 9 - 11, Japanese
    [Refereed]

  • Hiroshi Yamaguchi, Hiroaki Nagase, Masahiro Nishiyama, Shoichi Tokumoto, Yusuke Ishida, Kazumi Tomioka, Tsukasa Tanaka, Kyoko Fujita, Daisaku Toyoshima, Noriyuki Nishimura, Hiroshi Kurosawa, Kandai Nozu, Azusa Maruyama, Ryojiro Tanaka, Kazumoto Iijima
    OBJECTIVES: To evaluate the proportion of children presenting to the emergency department (ED) with altered mental status who demonstrate nonconvulsive seizures on reduced-lead electroencephalography (EEG), and to further investigate the characteristics, treatment, and outcomes in these patients compared with patients without nonconvulsive seizures. STUDY DESIGN: In this retrospective cohort study, we reviewed the database and medical records of pediatric patients (aged <18 years) in a single ED between May 1, 2016, and April 30, 2018. We first determined the proportion of nonconvulsive seizures among patients with altered mental status (Glasgow Coma Scale <15). We then compared the clinical presentation, demographic data, clinical diagnosis, EEG results, treatment, and outcomes of patients with altered mental status with nonconvulsive seizures and those without nonconvulsive seizures. RESULTS: In total, 16.9% of the patients with altered mental status (41 of 242; 95% CI, 12.2%-21.6%) evaluated by EEG had detectable nonconvulsive seizure, equivalent to 4.4% (41 of 932) of all patients with altered mental status presenting at our hospital. More than 80% of patients monitored for nonconvulsive seizures had a previous history of seizures, often febrile. Patients with nonconvulsive seizures were older (median, 68.5 vs 36.1 months) and had a higher Pediatric Cerebral Performance Category score at presentation (median, 2.0 vs 1.0). In addition, the proportion of patients admitted to the intensive care unit was significantly higher in the patients with nonconvulsive seizures (30.3% vs 15.0%). However, total duration of hospitalization, neurologic sequelae, and 30-day mortality rate did not differ between the 2 groups. CONCLUSIONS: A relatively high percentage of pediatric patients with altered mental status in the ED experience nonconvulsive seizures. The use of reduced-lead EEG monitoring in the ED might facilitate the recognition and treatment of nonconvulsive seizures, especially among patients with a history of seizures.
    Apr. 2019, The Journal of pediatrics, 207, 213 - 219, English, International magazine
    [Refereed]
    Scientific journal

  • 無症候性血尿にて長期経過の後に蛋白尿が出現し常染色体劣性Alport症候群の診断に至った1例
    青砥 悠哉, 南川 将吾, 石河 慎也, 榊原 菜々, 長野 智那, 藤村 順也, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 621 - 621, Japanese

  • クラリスロマイシンによりカルシニューリン阻害薬血中濃度の異常上昇をきたした2例
    市川 裕太, 南川 将吾, 青砥 悠哉, 石河 慎也, 榊原 菜々, 長野 智那, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 628 - 628, Japanese

  • Hashikami K, Asahina M, Nozu K, Iijima K, Nagata M, Takeyama M
    Mar. 2019, Biochemistry and biophysics reports, 17, 81 - 86
    [Refereed]

  • 腎生検後のADH上昇と生理食塩水輸液の安全性に関する検討
    石河 慎也, 野津 寛大, 青砥 悠哉, 榊原 菜々, 長野 智那, 南川 将吾, 山村 智彦, 飯島 一誠
    (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 217 - 217, Japanese

  • 先天性/乳児およびステロイド抵抗性ネフローゼ症候群における網羅的遺伝子診断体制
    長野 智那, 野津 寛大, 青砥 悠哉, 石河 慎也, 榊原 菜々, 南川 将吾, 山村 智彦, 飯島 一誠
    (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 217 - 217, Japanese

  • 急速に末期腎不全に至りSDCCAG8遺伝子異常を認めたネフロン癆関連ciliopathyの2歳男児
    渡邊 佳孝, 藤永 周一郎, 梅田 千里, 西野 智彦, 富井 祐治, 櫻谷 浩志, 村上 仁彦, 森貞 直哉, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 507 - 507, Japanese

  • 【マグネシウム代謝-その新たな臨床的意義】腎疾患とマグネシウム 低マグネシウム血症を呈する先天性腎疾患
    野津 寛大
    (株)東京医学社, Feb. 2019, 腎と透析, 86(2) (2), 195 - 199, Japanese
    [Refereed]

  • Kandai Nozu, Koichi Nakanishi, Yoshifusa Abe, Tomohiro Udagawa, Shinichi Okada, Takayuki Okamoto, Hiroshi Kaito, Katsuyoshi Kanemoto, Anna Kobayashi, Eriko Tanaka, Kazuki Tanaka, Taketsugu Hama, Rika Fujimaru, Saori Miwa, Tomohiko Yamamura, Natsusmi Yamamura, Tomoko Horinouchi, Shogo Minamikawa, Michio Nagata, Kazumoto Iijima
    Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.
    SPRINGER, Feb. 2019, Clinical and experimental nephrology, 23(2) (2), 158 - 168, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • China Nagano, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, Junya Fujimura, Nana Sakakibara, Keita Nakanishi, Tomoko Horinouchi, Yoichi Iwafuchi, Sentaro Kusuhara, Wataru Matsumiya, Norishige Yoshikawa, Kazumoto Iijima
    Transforming growth factor beta-induced (TGFBI)-associated corneal dystrophies are a group of inherited progressive corneal diseases. One of these TGFBI-associated corneal dystrophies is Avellino corneal dystrophy, an autosomal dominant corneal dystrophy characterized by multiple asymmetric stromal opacities that potentially impair vision. Recently, a case with corneal dystrophy complicated by nephropathy possessing a pathogenic variant of the TGFBI gene was reported for the first time. Here, we report the second case with the same condition and the same mutation in the TGFBI gene. The patient was an 18-year-old male. He and his father had already been diagnosed with corneal dystrophy. Proteinuria was revealed in the patient during urine screening at school. Since his serum creatinine level was raised, a percutaneous renal biopsy was performed. Light microscopy demonstrated oligomeganephronia. Electron microscopy demonstrated an irregular basement membrane. TGFBI was analyzed by direct sequencing. A heterozygous mutation c.371G > A in exon 4, which caused an amino acid substitution from arginine to histidine at codon 124, was identified in the patient and his father. Although only one case of TGFBI-associated corneal dystrophy and nephropathy has been reported, our case's clinical and pathological findings were almost identical to those in that reported case. Further investigations of this new disease entity should be reported to all nephrologists and ophthalmologists.
    Feb. 2019, CEN case reports, 8(1) (1), 14 - 17, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Kandai Nozu, Koichi Nakanishi, Yoshifusa Abe, Tomohiro Udagawa, Shinichi Okada, Takayuki Okamoto, Hiroshi Kaito, Katsuyoshi Kanemoto, Anna Kobayashi, Eriko Tanaka, Kazuki Tanaka, Taketsugu Hama, Rika Fujimaru, Saori Miwa, Tomohiko Yamamura, Natsusmi Yamamura, Tomoko Horinouchi, Shogo Minamikawa, Michio Nagata, Kazumoto Iijima
    Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.
    Feb. 2019, Clinical and experimental nephrology, 23(2) (2), 158 - 168, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Lee JM, Nozu K, Choi DE, Kang HG, Ha IS, Cheong HI
    Feb. 2019, Journal of clinical medicine, 8(2) (2)
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • Yosuke Inaguma, Atsutoshi Shiratori, Taku Nakagawa, Kyoko Kanda, Makiko Yoshida, Shigeo Hara, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa, Ryojiro Tanaka
    Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.
    Bentham Science Publishers, 2019, Open Urology and Nephrology Journal, 12(1) (1), 27 - 32, English
    Scientific journal

  • 偶発的に貧血、腎機能障害、高K血症が発見され、遺伝子検査でADTKD-RENと診断した男児例
    出来 沙織, 稲葉 彩, 出崎 緑, 内村 暢, 東 聡美, 町田 裕之, 大谷 方子, 森貞 直哉, 野津 寛大, 飯島 一誠, 伊藤 秀一, 城 謙輔, 山口 裕
    日本ベーリンガーインゲルハイム(株), 2019, 腎炎症例研究, 36, 150 - 162, Japanese

  • 偶発的に貧血、腎機能障害、高K血症が発見され、遺伝子検査でADTKD-RENと診断した男児例
    出来 沙織, 稲葉 彩, 出崎 緑, 内村 暢, 東 聡美, 町田 裕之, 大谷 方子, 森貞 直哉, 野津 寛大, 飯島 一誠, 伊藤 秀一, 城 謙輔, 山口 裕
    日本ベーリンガーインゲルハイム(株), 2019, 腎炎症例研究, 36, 150 - 162, Japanese
    [Refereed]

  • 【腎臓学 この一年の進歩】遺伝性腎疾患
    野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Jan. 2019, 日本腎臓学会誌, 61(1) (1), 18 - 22, Japanese
    [Refereed]

  • Hiroaki Hanafusa, Naoya Morisada, Tadashi Nomura, Daisuke Kobayashi, Yoshinobu Akasaka, Ming Juan Ye, Kandai Nozu, Noriyuki Nishimura, Kazumoto Iijima, Hideto Nakao
    CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and scoliosis/spinal malformation. It is caused by somatic mosaicism of gain-of-function variants of PIK3CA. Here, we describe a novel case of a 5-year-old Japanese girl with CLOVES and concurrent pancreatic steatosis. She had a recurrent somatic mutation in PIK3CA (NM_006218.3: c.1357G>A, p.Glu453Lys), elevated HbA1c levels, and pancreatic steatosis. This case indicates that pancreatic screening is critical for PIK3CA-related disorders.
    2019, Human genome variation, 6, 31 - 31, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nana Sakakibara, Naoya Morisada, Kandai Nozu, Koji Nagatani, Toshiyuki Ohta, Junya Shimizu, Takuzo Wada, Yuko Shima, Tomohiko Yamamura, Shogo Minamikawa, Junya Fujimura, Tomoko Horinouchi, China Nagano, Akemi Shono, Ming Juan Ye, Yoshimi Nozu, Koichi Nakanishi, Kazumoto Iijima
    Oral-facial-digital syndrome type 1 (OFD1) is a ciliopathy characterized by oral, facial, and digital malformations that are often accompanied by polycystic lesion of the kidney and central nervous involvement. OFD1 shows an X-linked recessive inheritance caused by mutation in the OFD1 gene (Xp22.2). The disease is generally considered embryonic lethal for hemizygous males. However, males with OFD1 mutations were recently reported. Here, we report four additional Japanese male patients with OFD1 variants and describe the variable clinical manifestation and disease severity among the four patients. Patient 1 with pathogenic indels including a 19-bp deletion and 4-bp insertion (c.2600-18_2600delinsACCT) had end-stage renal disease (ESRD) with bilateral cystic kidneys and sensory hearing loss. He showed neither intellectual disability nor facial or digital dysmorphism. Patient 2 with a missense variant in exon 7 (c.539 A > T, p.Asp180Val) presented head circumference enlargement, brachydactyly, high-arched palate, micropenis, severe global developmental delay, and ESRD. Patient 3 had a single base substitution at the splice donor site of intron 16 (c.2260 + 2 T > G) causing a 513-bp deletion at the transcript level. The patient had chronic kidney disease and speech delay, but no oral, facial, or digital dysmorphism. His uncle (patient 4) carried the same OFD1 variant and showed ESRD with extra-renal malformations including obesity and micropenis, which was previously diagnosed as Bardet-Biedl syndrome. The OFD1 mutations were not lethal in these four male patients, likely because the three mutations were in-frame or missense. This report provided insights into the onset mechanism and phenotype-genotype association in patients with OFD1 mutations.
    Jan. 2019, Journal of human genetics, 64(1) (1), 3 - 9, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Masahiro Nishiyama, Yuichi Takami, Yusuke Ishida, Kazumi Tomioka, Tsukasa Tanaka, Hiroaki Nagase, Taku Nakagawa, Shoichi Tokumoto, Hiroshi Yamaguchi, Daisaku Toyoshima, Azusa Maruyama, Kandai Nozu, Noriyuki Nishimura, Kazumoto Iijima
    Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.
    Jan. 2019, Epilepsy & behavior : E&B, 90, 15 - 19, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Junya Fujimura, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, Keita Nakanishi, Tomoko Horinouchi, China Nagano, Nana Sakakibara, Koichi Nakanishi, Yuko Shima, Kenichi Miyako, Yoshimi Nozu, Naoya Morisada, Hiroaki Nagase, Takeshi Ninchoji, Hiroshi Kaito, Kazumoto Iijima
    Introduction: Gitelman syndrome (GS) is a tubulopathy exhibited by salt loss. GS cases are most often diagnosed by chance blood test. Aside from that, some cases are also diagnosed from tetanic symptoms associated with hypokalemia and/or hypomagnesemia or short stature. As for complications, thyroid dysfunction and short stature are known, but the incidence rates for these complications have not yet been elucidated. In addition, no genotype-phenotype correlation has been identified in GS. Methods: We examined the clinical characteristics and genotype-phenotype correlation in genetically proven GS cases with homozygous or compound heterozygous variants in SLC12A3 (n = 185). Results: In our cohort, diagnostic opportunities were by chance blood tests (54.7%), tetany (32.6%), or short stature (7.2%). Regarding complications, 16.3% had short stature, 13.7% had experienced febrile convulsion, 4.3% had thyroid dysfunction, and 2.5% were diagnosed with epilepsy. In one case, QT prolongation was detected. Among 29 cases with short stature, 10 were diagnosed with growth hormone (GH) deficiency and GH replacement therapy started. Interestingly, there was a strong correlation in serum magnesium levels between cases with p.Arg642Cys and/or p.Leu858His and cases without these variants, which are mutational hotspots in the Japanese population (1.76 mg/dl vs. 1.43 mg/dl, P < 0.001). Conclusion: This study has revealed, for the first time, clinical characteristics in genetically proven GS cases in the Japanese population, including prevalence of complications. Patients with hypokalemia detected by chance blood test should have gene tests performed. Patients with GS need attention for developing extrarenal complications, such as short stature, febrile convulsion, thyroid dysfunction, epilepsy, or QT prolongation. It was also revealed for the first time that hypomagnesemia was not severe in some variants in SLC12A3.
    Jan. 2019, Kidney international reports, 4(1) (1), 119 - 125, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Goda T, Komatsu H, Nozu K, Nakajima H
    Hypomagnesemia 1 (HOMG1) is an extremely rare disease with autosomal recessive inheritance that is caused by mutations in the transient receptor potential melastatin 6 gene (TRPM6). Here, we describe a pediatric HOMG1 case with novel compound heterozygous mutations of TRPM6 (c.1483 C > T [p.Gln495*] and c.2715del [p.Trp905*]) in a 2-month-old boy who developed refractory seizures due to hypomagnesemia with secondary hypocalcemia.
    2019, Human genome variation, 6, 13 - 13, English, International magazine
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • 飯島 一誠, 堀之内 智子, 野津 寛大
    (株)東京医学社, Dec. 2018, 腎と透析, 85(6) (6), 777 - 781, Japanese

  • 渡邉 駿, 小黒 昌彦, 鳥生 直哉, 稲永 亮平, 小澤 祐子, 井熊 大輔, 大島 洋一, 水野 裕基, 関根 章成, 川田 真宏, 早見 典子, 住田 圭一, 平松 里佳子, 山内 真之, 長谷川 詠子, 諏訪部 達也, 星野 純一, 澤 直樹, 乳原 善文, 高市 憲明, 田中 希穂, 松波 昌寿, 中村 有紀, 石井 保夫, 野崎 裕美, 土谷 良樹, 野津 寛大, 藤井 晶子, 藤井 丈士, 大橋 健一, 金綱 友木子, 宮崎 陽一
    (株)東京医学社, Dec. 2018, 腎と透析, 85(6) (6), 869 - 879, Japanese

  • 男性腎不全の家族歴からネフロン癆関連シリオパチーの診断に至った3歳男児例
    和田 卓三, 島 友子, 浜 武継, 向山 弘展, 鈴木 啓之, 森貞 直哉, 野津 寛大, 飯島 一誠, 中西 浩一
    和歌山医学会, Dec. 2018, 和歌山医学, 69(4) (4), 202 - 202, Japanese
    [Refereed]

  • Shogo Minamikawa, Kandai Nozu, Shingo Maeta, Tomohiko Yamamura, Keita Nakanishi, Junya Fujimura, Tomoko Horinouchi, China Nagano, Nana Sakakibara, Hiroaki Nagase, Hideaki Shima, Kenta Noda, Takeshi Ninchoji, Hiroshi Kaito, Kazumoto Iijima
    CD80, which regulates T cell activation, may provide a differential diagnostic marker between minimal change disease (MCD) and other renal diseases, including focal segmental glomerular sclerosis (FSGS). However, recent reports show contrasting results. Therefore, we evaluated the utility of urinary CD80 as a diagnostic biomarker. We collected 65 urine samples from 55 patients with MCD (n = 31), FSGS (n = 4), inherited nephrotic syndrome (n = 4), Alport syndrome (n = 5) and other glomerular diseases (n = 11), and control samples (n = 30). We measured urinary CD80 levels by ELISA. Urinary CD80 (ng/gCr) (median, interquartile range) levels were significantly higher in patients with MCD in relapse (91.5, 31.1-356.0), FSGS (376.2, 62.7-1916.0), and inherited nephrotic syndrome (220.1, 62.9-865.3), than in patients with MCD in remission (29.5, 21.7-52.8) (p < 0.05). Elevation of urinary CD80 was observed, even in patients with inherited nephrotic syndrome unrelated to T cell activation. Additionally, urinary CD80 was positively correlated with urinary protein levels. Our results suggest that urinary CD80 is unreliable as a differential diagnostic marker between MCD in relapse and FSGS or inherited kidney diseases. Increased urinary CD80 excretion was present in all patients with active kidney disease.
    Nov. 2018, Scientific reports, 8(1) (1), 17322 - 17322, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 榊原 菜々, 森貞 直哉, 長野 智那, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 山村 智彦, 貝藤 裕史, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2018, 日本小児腎臓病学会雑誌, 31(2) (2), 175 - 175, Japanese

  • 長野 智那, 野津 寛大, 森貞 直哉, 松村 千恵子, 榊原 菜々, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2018, 日本小児腎臓病学会雑誌, 31(2) (2), 176 - 176, Japanese

  • Masahiro Nishiyama, Hiroaki Nagase, Kazumi Tomioka, Tsukasa Tanaka, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Kyoko Fujita, Azusa Maruyama, Hiroshi Kurosawa, Yoshiyuki Uetani, Kandai Nozu, Mariko Taniguchi-Ikeda, Ichiro Morioka, Satoshi Takada, Kazumoto Iijima
    BACKGROUND: Fosphenytoin (fPHT) and continuous intravenous midazolam (cMDL) had commonly been used as second-line treatments for pediatric status epilepticus (SE) in Japan. However, there is no comparative study of these two treatments. METHODS: We included consecutive children who 1) were admitted to Kobe Children's Hospital because of convulsion with fever and 2) were treated with either fPHT or cMDL as second-line treatment for convulsive SE lasting for longer than 30 min. We compared, between the fPHT and cMDL groups, the proportion of barbiturate coma therapy (BCT), incomplete recovery of consciousness, mechanical ventilation, and inotropic agents. RESULTS: The proportion of BCT was not significantly different between the two groups (48.7% [20/41] in fPHT and 35.3% [29/82] in cMDL, p = 0.17). The prevalence of incomplete recovery of consciousness, mechanical ventilation, and inotropic agents was not different between the two groups. After excluding 49 patients treated with BCT, incomplete recovery of consciousness 6 h and 12 h after onset was more frequent in the cMDL group than in the fPHT group (71.7% vs. 33.3%, p < 0.01; 56.6% vs. 14.2%, p < 0.01; respectively). Mechanical ventilation was more frequent in the cMDL group than in the fPHT group (32.0% vs. 4.7%, p = 0.01). CONCLUSIONS: Our results suggest that 1) the efficacy of fPHT and cMDL is similar, although cMDL may prevent the need for BCT compared with fPHT, and 2) fPHT is relatively safe as a second-line treatment for pediatric SE in patients who do not require BCT.
    Nov. 2018, Brain & development, 40(10) (10), 884 - 890, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoko Horinouchi, Mayumi Sako, Koichi Nakanishi, Kenji Ishikura, Shuichi Ito, Hidefumi Nakamura, Mari Saito Oba, Kandai Nozu, Kazumoto Iijima
    BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Approximately 80-90% of patients with childhood INS have steroid-sensitive nephrotic syndrome (SSNS), and can obtain remission with steroid therapy, while the remainder have steroid-resistant nephrotic syndrome (SRNS). Furthermore, approximately 50% of children with SSNS develop frequently-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS/SDNS are usually treated with immunosuppressive agents such as cyclosporine, cyclophosphamide, or mizoribine in Japan. However, 10-20% of children receiving immunosuppressive agents still show frequent relapse and/or steroid dependence during or after treatment, which is defined as complicated FRNS/SDNS. Furthermore, 30% of SRNS patients who obtain remission after additional treatments such as cyclosporine also turn out to be complicated FRNS/SDNS. For such complicated FRNS/SDNS patients, rituximab (RTX) is currently used; however, recurrence after RTX treatment also remains an open issue. Because long-term use of existing immunosuppressive drugs has limitations, development of a novel treatment for maintenance therapy after RTX is desirable. Mycophenolate mofetil (MMF) is an immunosuppressive drug with fewer side effects than cyclosporine or cyclophosphamide. Importantly, recent studies have reported the efficacy of MMF in children with nephrotic syndrome. METHODS: We conduct a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of MMF after RTX therapy in children with complicated FRNS/SDNS. Patients are allocated to either RTX plus MMF treatment group, or RTX plus placebo treatment group. For the former group, MMF is administered at a dose of 1000-1200 mg/m2/day (maximum 2 g/day) twice daily for 17 months after RTX treatment. The primary endpoint is time-to-treatment failure (development of frequent relapses, steroid dependence or steroid resistance). DISCUSSION: The results will provide important data on the use of MMF as maintenance therapy after RTX to prevent complicated FRNS/SDNS patients from declining into treatment failure. In future, MMF in conjunction with RTX treatment may permit increased duration of remission in 'complicated' FRNS/SDNS cases. TRIAL REGISTRATION: This trial was prospectively registered to UMIN Clinical Trials Registry on June 23, 2014 (UMIN Trial ID: UMIN000014347 ).
    Nov. 2018, BMC nephrology, 19(1) (1), 302 - 302, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ishimori S, Kaito H, Shima Y, Kamioka I, Hamahira K, Nozu K, Nakanishi K, Tanaka R, Yoshikawa N, Iijima K
    Objectives: Acute kidney injury (AKI) at onset of adult systemic lupus erythematosus (SLE) is a risk factor for end stage kidney disease (ESKD). However, data on childhood-onset lupus nephritis (LN) with AKI are scarce.Methods: We retrospectively reviewed the complete files of pediatric SLE patients from 1995 to 2010. All patients underwent kidney biopsy promptly after diagnosis.Results: Thirty-six patients (10 males and 26 females) were enrolled. Mean age at diagnosis and observation period were 11.6 ± 2.4 and 8.1 ± 4.4 years, respectively. Seven patients had AKI at onset of SLE. Compared with those without AKI, patients with AKI had significantly higher proportions of pathologically proliferative LN. Only one patient with AKI progressed to ESKD without complete recovery of renal function. Overall and renal survival rates were 100and 97.2%, respectively. There was no significant difference in estimated glomerular filtration rate at the final visit (85ml/min/1.73 m2 in the AKI group vs. 103.2 ml/min/1.73 m2 in the non-AKI group; p = .11).Conclusion: Our study demonstrated favorable renal outcomes in childhood-onset LN with AKI in the near to midterm period. Inducing complete remission may be important for preserving renal function.
    Oct. 2018, Modern rheumatology, 29(6) (6), 1 - 17, English, International magazine
    [Refereed]
    Scientific journal

  • Aya Imafuku, Kandai Nozu, Naoki Sawa, Eiko Hasegawa, Rikako Hiramatsu, Masahiro Kawada, Junichi Hoshino, Kiho Tanaka, Yasuo Ishii, Kenmei Takaichi, Takeshi Fujii, Kenichi Ohashi, Kazumoto Iijima, Yoshifumi Ubara
    AIM: Type IV collagen nephropathies include Alport Syndrome and thin basement membrane nephropathy (TBMN), which are caused by mutations in COL4A3/A4/A5 genes. Recently, reports of patients with heterozygous mutations in COL4A3/A4 have been increasing. The clinical course of these patients has a wide variety, and they are diagnosed as TBMN, autosomal dominant Alport syndrome (ADAS), or familial focal segmental glomerular sclerosis. However, diagnosis, frequency and clinicopathological manifestation of them remains unclear. We tested COL4A3/A4/A5 genes in patients with hereditary nephritis that was difficult to diagnose clinicopathologically, and investigated who should undergo such testing. METHODS: We performed immunostaining for α5 chain of type IV collagen [α5 (IV)] in 27 patients from 21 families who fitted the following criteria: (i) haematuria and proteinuria (± renal dysfunction); (ii) family history of haematuria, proteinuria, and/or renal dysfunction (autosomal dominant inheritance); (iii) no specific glomerulonephritis; and (iv) thinning, splitting, or lamellation of the glomerular basement membrane (GBM) on electron microscopy. Then we performed genetic testing in 19 patients from 16 families who showed normal α5 (IV) patterns. We conducted a retrospective analysis of their clinicopathological findings. RESULTS: Among 16 families, 69% were detected heterozygous mutations in COL4A3/A4, suggesting the diagnosis of TBMN/ADAS. Twenty-one percent of patients developed end stage renal disease. All patients showed thinning of GBM, which was accompanied by splitting or lamellation in seven patients. CONCLUSION: A considerable fraction of patients with hereditary nephritis that is difficult to diagnose clinicopathologically have TBMN/ADAS. It is important to recognize TBMN/ADAS and perform genetic testing in appropriate patients.
    Oct. 2018, Nephrology (Carlton, Vic.), 23(10) (10), 940 - 947, English, International magazine
    [Refereed]
    Scientific journal

  • Taketsugu Hama, Koichi Nakanishi, Kenji Ishikura, Shuichi Ito, Hidefumi Nakamura, Mayumi Sako, Mari Saito-Oba, Kandai Nozu, Yuko Shima, Kazumoto Iijima, Norishige Yoshikawa
    BACKGROUND: Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS. METHODS/DESIGN: We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse. DISCUSSION: The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone. TRIAL REGISTRATION: UMIN000005103 , (Prospectively registered 1st March 2011).
    Sep. 2018, BMC nephrology, 19(1) (1), 223 - 223, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 大山 紀子, 大久保 一宏, 一宮 優子, 井上 雅崇, 碇 航太, トカン・ヴラッド, 戸田 尚子, 石井 加奈子, 白石 暁, 西山 慶, 野津 寛大, 大賀 正一
    (一社)日本内分泌学会, Sep. 2018, 日本内分泌学会雑誌, 94(2) (2), 700 - 700, Japanese

  • Nakanishi K, Kaito H, Ogi M, Takai D, Fujimura J, Horinouchi T, Yamamura T, Minamikawa S, Ninchoji T, Nozu K, Imadome KI, Iijima K
    Sep. 2018, Case reports in nephrology and dialysis, 8(3) (3), 198 - 206
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima
    Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown.Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay.Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10-23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10-25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10-9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10-12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10-11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor.Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.
    Aug. 2018, Journal of the American Society of Nephrology : JASN, 29(8) (8), 2189 - 2199, English, International magazine
    [Refereed]
    Scientific journal

  • 蛋白尿出現から2年の経過で末期腎不全に至ったTRPC6遺伝子変異による遺伝性FSGSの一男児例
    松村 英樹, 山崎 哲司, 芦田 明, 藤井 裕子, 白数 明彦, 中倉 兵庫, 野津 寛大, 飯島 一誠, 玉井 浩
    (一社)日本腎臓学会, Aug. 2018, 日本腎臓学会誌, 60(6) (6), 735 - 735, Japanese

  • Charcot-Marie-Tooth病を合併しINF2遺伝子変異が同定された遺伝性FSGSの1例
    山崎 哲司, 芦田 明, 松村 英樹, 藤井 裕子, 白数 明彦, 中倉 兵庫, 野津 寛大, 飯島 一誠, 玉井 浩
    (一社)日本腎臓学会, Aug. 2018, 日本腎臓学会誌, 60(6) (6), 735 - 735, Japanese

  • China Nagano, Kandai Nozu, Naoya Morisada, Masahiko Yazawa, Daisuke Ichikawa, Keita Numasawa, Hiroyo Kourakata, Chieko Matsumura, Satoshi Tazoe, Ryojiro Tanaka, Tomohiko Yamamura, Shogo Minamikawa, Tomoko Horinouchi, Keita Nakanishi, Junya Fujimura, Nana Sakakibara, Yoshimi Nozu, Ming Juan Ye, Hiroshi Kaito, Kazumoto Iijima
    BACKGROUND: Comprehensive genetic approaches for diagnosing inherited kidney diseases using next-generation sequencing (NGS) have recently been established. However, even with these approaches, we are still failing to detect gene defects in some patients who appear to suffer from genetic diseases. One of the reasons for this is the difficulty of detecting copy number variations (CNVs) using our current approaches. For such cases, we can apply methods of array-based comparative genomic hybridization (aCGH) or multiplex ligation and probe amplification (MLPA); however, these are expensive and laborious and also often fail to identify CNVs. Here, we report seven cases with CNVs in various inherited kidney diseases screened by NGS pair analysis. METHODS: Targeted sequencing analysis for causative genes was conducted for cases with suspected inherited kidney diseases, for some of which a definitive genetic diagnosis had not been achieved. We conducted pair analysis using NGS data for those cases. When CNVs were detected by pair analysis, they were confirmed by aCGH and/or MLPA. RESULTS: In seven cases, CNVs in various causative genes of inherited kidney diseases were detected by pair analysis. With aCGH and/or MLPA, pathogenic CNV variants were confirmed: COL4A5 or HNF1B in two cases each, and EYA1, CLCNKB, or PAX2 in one each. CONCLUSION: We presented seven cases with CNVs in various genes that were screened by pair analysis. The NGS-based CNV detection method is useful for comprehensive screening of CNVs, and our results revealed that, for a certain proportion of cases, CNV analysis is necessary for accurate genetic diagnosis.
    Aug. 2018, Clinical and experimental nephrology, 22(4) (4), 881 - 888, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kazumi Tomioka, Hiroaki Nagase, Tsukasa Tanaka, Masahiro Nishiyama, Hiroshi Yamaguchi, Yusuke Ishida, Daisaku Toyoshima, Azusa Maruyama, Kyoko Fujita, Mariko Taniguchi-Ikeda, Kandai Nozu, Ichiro Morioka, Noriyuki Nishimura, Hiroshi Kurosawa, Yoshiyuki Uetani, Kazumoto Iijima
    BACKGROUND: Children who present with seizure and/or impaired consciousness accompanied by fever without known etiology (SICF) may be diagnosed with either acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of AE cases are fatal, it is difficult to identify fatal cases among children with SICF, which are often critical by the time of diagnosis. Thus, early prediction of outcomes for children with SICF, prior to diagnosis, may help to reduce mortality associated with AE. The aim of the present study was to identify clinical and laboratory risk factors for mortality acquired within 6 h of onset among children with SICF. METHODS: We retrospectively reviewed the medical records of children who had been admitted to Kobe Children's Hospital (Kobe, Japan) with SICF between October 2002 and September 2015. We compared clinical and laboratory characteristics acquired within 6 h of onset and outcomes between survivors and non-survivors using univariate and multivariate analyses. RESULTS: The survivor and non-survivor groups included 659 and nine patients, respectively. All patients in the non-survivor group received a final diagnosis of AE. Univariate analysis revealed significant differences between the groups with regard to seizure duration and the following laboratory parameters: aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase, sodium, and lactate. The multivariate analysis identified AST as a significant independent factor associated with mortality. CONCLUSIONS: Elevation of AST within 6 h of onset is independently correlated with mortality in children with SICF. Our result may elucidate earlier intervention for patients with high risk of mortality.
    Aug. 2018, Brain & development, 40(7) (7), 552 - 557, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoko Horinouchi, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, Takashi Omori, Keita Nakanishi, Junya Fujimura, Akira Ashida, Mineaki Kitamura, Mitsuhiro Kawano, Wataru Shimabukuro, Chizuko Kitabayashi, Aya Imafuku, Keiichi Tamagaki, Koichi Kamei, Kenjirou Okamoto, Shuichiro Fujinaga, Masafumi Oka, Toru Igarashi, Akinori Miyazono, Emi Sawanobori, Rika Fujimaru, Koichi Nakanishi, Yuko Shima, Masafumi Matsuo, Ming Juan Ye, Yoshimi Nozu, Naoya Morisada, Hiroshi Kaito, Kazumoto Iijima
    BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS. METHODS: We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating (n=21, from 14 families) and nontruncating (n=25, from 15 families) mutations at the transcript level. RESULTS: We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns (n=14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations (P=0.001). CONCLUSIONS: We report unpredictable atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations.
    Aug. 2018, Journal of the American Society of Nephrology : JASN, 29(8) (8), 2244 - 2254, English, International magazine
    [Refereed]
    Scientific journal

  • Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima
    Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown.Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay.Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10-23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10-25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10-9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10-12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10-11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor.Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.
    Aug. 2018, Journal of the American Society of Nephrology : JASN, 29(8) (8), 2189 - 2199, English, International magazine
    [Refereed]
    Scientific journal

  • Arima M, Tsukamoto S, Akiyama R, Nishiyama K, Kohno RI, Tachibana T, Hayashida A, Murayama M, Hisatomi T, Nozu K, Iijima K, Ohga S, Sonoda KH
    Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities. The ocular findings in Pierson syndrome are not well understood, because the incidence of this syndrome is very rare. We report ocular findings in a 5-month-old boy with Pierson syndrome with a novel mutation in LAMB2. We performed a pupilloplasty for his microcoria. Ophthalmic examinations after surgery revealed that he had cataract, severe retinal degeneration, and high myopia. Optical coherence tomography showed the collapse of retinal layer structures and a marked decrease of choroidal thickness. Immunohistochemistry and electron microscopy examinations revealed abnormal iris differentiation and thinning or defect of basal membranes. These results suggest that the development of the iris, lens, retina, and choroid are affected in this type of mutation.
    Aug. 2018, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus, 22(5) (5), 401 - 403.e1, English, International magazine
    [Refereed]
    Scientific journal

  • 治療方針の決定に疾患パネル解析を用いたステロイド抵抗性ネフローゼ症候群の1例
    NAGANO CHINA, KAITO HIROSHI, FUJIMURA JUNYA, HORINOUCHI TOMOKO, NAKANISHI KEITA, MINAMIKAWA SHOGO, YAMAMURA TOMOHIKO, NOZU KANDAI, IIJIMA KAZUMOTO, KAMIYOSHI NAOHIRO, 濱平 陽史
    Jul. 2018, 日本小児腎不全学会雑誌, 38, 148 - 151, Japanese
    [Refereed]
    Scientific journal

  • Watanabe S, Aizawa T, Tsukaguchi H, Tsugawa K, Tsuruga K, Shono A, Nozu K, Iijima K, Joh K, Tanaka H
    Recent advances in high-throughput sequencing for clinical genetic testing have revealed novel disease-causing genes, such as Crumbs homolog 2 (CRB2) for early-onset steroid-resistant nephrotic syndrome (SRNS). We report the long-term clinicopathologic observation of a Japanese female patient with SRNS caused by a newly identified compound heterozygous mutation of CRB2 (p.Arg628Cys and p.Gly839Trp located in the 10th and 11th epidermal growth factor-like domains, respectively). She was initially examined during a mass urinary screening for 3.5-year-old children in Japan. Although she developed long-standing SRNS without any extrarenal clinical signs thereafter, her renal function was well-preserved over the next 17 years. In total, six sequential renal biopsy specimens revealed histologic alterations ranging from minor glomerular abnormalities to advanced focal segmental glomerulosclerosis (FSGS). A genetic analysis for SRNS performed at 19 years of age revealed a newly identified compound heterozygous mutation in CRB2. Glomerular CRB2 immunoreactivity in biopsy specimens from the patient was scanty, whereas intense expression was observed in those from patients with idiopathic FSGS or in controls. To our knowledge, this is the first report regarding a long-term outcome in a case of SRNS due to an identified CRB2 mutation. Although the phenotype of CRB2 mutation-related syndrome is now expanding, we believe that this case might provide a novel clinicopathologic aspect of this syndrome.
    Jul. 2018, Nephrology (Carlton, Vic.), 23(7) (7), 697 - 702, English, International magazine
    [Refereed]
    Scientific journal

  • Natsuki Matsunoshita, Kandai Nozu, Masahide Yoshikane, Azusa Kawaguchi, Naoya Fujita, Naoya Morisada, Shingo Ishimori, Tomohiko Yamamura, Shogo Minamikawa, Tomoko Horinouchi, Keita Nakanishi, Junya Fujimura, Takeshi Ninchoji, Ichiro Morioka, Hiroaki Nagase, Mariko Taniguchi-Ikeda, Hiroshi Kaito, Kazumoto Iijima
    Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.
    Jul. 2018, Journal of human genetics, 63(8) (8), 887 - 892, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Horike K, Takeda A, Tsujita M, Goto N, Watarai Y, Uchida K, Katayama A, Nishihira M, Shimizu A, Nozu K, Morozumi K
    Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.
    Jul. 2018, Nephrology (Carlton, Vic.), 23 Suppl 2, 17 - 21, English, International magazine
    [Refereed]
    Scientific journal

  • Shima Y, Nakanishi K, Kaku Y, Ishikura K, Hataya H, Matsuyama T, Honda M, Sako M, Nozu K, Tanaka R, Iijima K, Yoshikawa N, Japanese Pediatric IgA Nephropathy Treatment, Study Group
    BACKGROUND: Two previous randomized controlled trials showed that treatment of severe childhood immunoglobulin A (IgA) nephropathy using prednisolone with azathioprine, heparin-warfarin, or dipyridamole prevented the increase of sclerosed glomeruli. Prednisolone alone, however, did not prevent further increase. These studies indicated the importance of immunosuppressants in the treatment. An additional pilot study using mizoribine instead of azathioprine enabled us to complete 2 years of combined regimen. It showed non-numerical inferior effectiveness compared with the azathioprine regimen. Further examination of the additional efficacy of warfarin and dipyridamole was required. METHODS: A randomized control trial of prednisolone and mizoribine with (group 1) or without (group 2) warfarin and dipyridamole was administered for treatment of 71 children with severe IgA nephropathy to evaluate the efficacy of additional warfarin and dipyridamole. RESULTS: Thirty of 34 patients (88.2%) in group 1, and 27 of 36 patients (75.0%) showed the disappearance of proteinuria as defined by early morning urinary protein to creatinine ratio of < 0.2 during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method showed that the disappearance rate of proteinuria was significantly higher in group 1 than in group 2 (log-rank P = 0.04). There was no significant difference in pathological findings, but there was a tendency of increase of global sclerosis in group1 which might be related to warfarin. Most of the adverse effects were related to prednisolone, but fortunately transient. CONCLUSIONS: The balance between minimal benefits of warfarin/dipyridamole and potential adverse effects may be in favor of avoiding them in children with IgA nephropathy.
    Jul. 2018, Pediatric nephrology (Berlin, Germany), 33(11) (11), 2103 - 2112, English, International magazine
    [Refereed]
    Scientific journal

  • Okamoto T, Nozu K, Iijima K, Ariga T
    Jul. 2018, Journal of nephrology, 32(1) (1), 155 - 159
    [Refereed]

  • 高血圧を呈さず高度蛋白尿が遷延した溶連菌感染後急性糸球体腎炎の1例
    藤村 順也, 貝藤 裕史, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 野津 寛大, 飯島 一誠
    症例は8歳の女児で、肉眼的血尿を主訴に前医を受診した。1kg(+5%)の体重増加と上眼瞼の浮腫を認めたが、高血圧はなかった。肉眼的血尿と高度蛋白尿に加え、腎機能障害、低補体血症、低アルブミン血症を認めた。APSGNとして保存的加療が開始されたが、腎機能障害と乏尿が改善せず当院に転院となった。転院後もネフローゼレベルの蛋白尿と腎機能障害が遷延したため第14病日に腎生検を行った。光顕所見ではびまん性の管内細胞増殖と係蹄壁の二重化およびメサンギウム細胞増殖を認め、また40%の糸球体に線維細胞性半月体を認めた。免疫染色でC3の顆粒状沈着と電子顕微鏡所見でhumpを認めたことから、APSGNと確定診断した。メチルプレドニゾロンパルス療法を施行したところ発症後1ヵ月で腎機能は正常化し、また3ヵ月で尿蛋白は陰性化した。転院後も高血圧を呈することはなかった。APSGNにおける高血圧の発症機序は一般に、ナトリウム・水貯留によるhypervolemiaで説明される。本症例では経過を通じ溢水所見を呈したことはなく、これは血圧の推移と矛盾しない。しかしその一方で、腎機能の推移や腎病理所見からは腎性の要素で高血圧を呈する危険性も十分に考えられた。APSGNではまれとされる高度蛋白尿が病態を修飾した可能性も考えられた。溢水所見や血圧上昇を認めないAPSGNであっても体液量管理は慎重に行う必要がある。(著者抄録)
    日本小児高血圧研究会, Jun. 2018, 日本小児高血圧研究会誌, 15(1) (1), 21 - 25, Japanese

  • Tomohiko Yamamura, Kandai Nozu, Hiroaki Ueda, Rika Fujimaru, Ryutaro Hisatomi, Yoko Yoshida, Hideki Kato, Masaomi Nangaku, Toshiyuki Miyata, Toshihiro Sawai, Shogo Minamikawa, Hiroshi Kaito, Masafumi Matsuo, Kazumoto Iijima
    Pathogenic variants in specific complement-related genes lead to atypical hemolytic uremic syndrome (aHUS). Some reports have indicated that patients with digenic variants in these genes might present severer phenotypes. Upon detecting novel intronic variants, transcriptional analysis is necessary to prove pathogenicity; however, when intronic variants are located in intron 1 and, as a result, no transcript is produced, no appropriate method had been established to reveal the pathogenicity. Recently, the minigene assay was used to assess the pathogenicity of intronic variants. Here, we report an infantile case of aHUS caused by digenic mutations in two different complement-related genes, C3 and MCP. Targeted sequencing detected a known variant in C3 and a novel variant in the intron 1 splicing donor site of MCP. To assess the pathogenicity of this intronic variant, we conducted functional splicing assay using a minigene construct and quantitative PCR analysis of the MCP transcript, revealing the pathogenicity of the intronic variant. In conclusion, the minigene assay revealed the pathogenicity of the intron 1 splicing donor site variant for the first time. This case showed a severe phenotype of infantile-onset aHUS associated with digenic variants in two complement-related genes.
    Jun. 2018, Journal of human genetics, 63(6) (6), 755 - 759, English, International magazine
    [Refereed]
    Scientific journal

  • Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
    No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.
    May 2018, Nature communications, 9(1) (1), 1960 - 1960, English, International magazine
    [Refereed]
    Scientific journal

  • 藤村 順也, 野津 寛大, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    症例1(6歳男児)、症例2(13歳男児)。両症例とも低身長を主訴に当院へ紹介となった。受診時、いずれの症例も血液検査では低K血症、代謝性アルカローシスを認めたが、血清Mgの低下は認めなかった。遺伝子検査の結果、SLC12A3遺伝子に複合ヘテロ接合体変異が確認され、Gitelman症候群と確定診断されたた。症例1はカリウム補充治療開始後1年が経過し、身長のcatch-up傾向を認めている。症例2はカリウム補充とGH補充療法を同時に開始し、catch-upを認めている。
    日本小児体液研究会, May 2018, 日本小児体液研究会誌, 10, 67 - 72, Japanese

  • 堀之内 智子, 山村 智彦, 榊原 菜々, 長野 智那, 藤村 順也, 中西 啓太, 南川 将吾, 貝藤 裕史, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 99 - 99, Japanese

  • 榊原 菜々, 森貞 直哉, 長野 智那, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 山村 智彦, 貝藤 裕史, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 100 - 100, Japanese

  • 長野 智那, 野津 寛大, 森貞 直哉, 松村 千恵子, 榊原 菜々, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 101 - 101, Japanese

  • 辻 ゆり佳, 山村 智彦, 野津 寛大, 榊原 菜々, 長野 智那, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 147 - 147, Japanese

  • 南川 将吾, 野津 寛大, 前田 真吾, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 藤村 順也, 山村 智彦, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 156 - 156, Japanese

  • 藤村 順也, 野津 寛大, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 200 - 200, Japanese

  • 島 友子, 中西 浩一, 浜 武継, 田中 侑, 佐藤 匡, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 鈴木 啓之, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 170 - 170, Japanese

  • 男性腎不全の家族歴からネフロン癆関連シリオパチーの診断に至った3歳男児例
    和田 卓三, 島 友子, 田中 侑, 佐藤 匡, 浜 武継, 向山 弘展, 鈴木 啓之, 森貞 直哉, 野津 寛大, 飯島 一誠, 中西 浩一
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 166 - 166, Japanese
    [Refereed]

  • Shogo Minamikawa, Kandai Nozu, Yoshimi Nozu, Tomohiko Yamamura, Mariko Taniguchi-Ikeda, Keita Nakanishi, Junya Fujimura, Tomoko Horinouchi, Yuko Shima, Koichi Nakanishi, Masuji Hattori, Kyoko Kanda, Ryojiro Tanaka, Naoya Morisada, China Nagano, Nana Sakakibara, Hiroaki Nagase, Ichiro Morioka, Hiroshi Kaito, Kazumoto Iijima
    The pattern of X-chromosome inactivation (XCI) can affect the clinical severity of X-linked disorders in females. XCI pattern analysis has been conducted mainly by HUMARA assay, a polymerase chain reaction-based assay using a methylation-sensitive restriction enzyme. However, this assay examines the XCI ratio of the androgen receptor gene at the genomic DNA level and does not reflect the ratio of either targeted gene directly or at the mRNA level. Here, we report four females with Dent disease, and we clarified the correlation between XCI and female cases of Dent disease using not only HUMARA assay but also a novel analytical method by RNA sequencing. We constructed genetic analysis for 4 female cases showing high level of urinary low-molecular-weight proteinuria and their parents. Their XCI pattern was analyzed by both HUMARA assay and an ultra-deep targeted RNA sequencing of the CLCN5 gene using genomic DNA and mRNA extracted from both leukocytes and urine sediment. All four cases possessed pathogenic variants of the CLCN5 gene. XCI analysis revealed skewed XCI in only two cases, while the other two showed random XCI. All assay results of HUMARA and targeted RNA sequencing in both leukocytes and urinary sediment were clearly identical in all four cases. We developed a novel XCI analytical assay of ultra-deep targeted RNA sequencing and revealed that skewed XCI explains the mechanism of onset of female Dent disease in only half of such cases.
    May 2018, Journal of human genetics, 63(5) (5), 589 - 595, English, International magazine
    [Refereed]
    Scientific journal

  • Ai Unzaki, Naoya Morisada, Kandai Nozu, Ming Juan Ye, Shuichi Ito, Tatsuo Matsunaga, Kenji Ishikura, Shihomi Ina, Koji Nagatani, Takayuki Okamoto, Yuji Inaba, Naoko Ito, Toru Igarashi, Shoichiro Kanda, Ken Ito, Kohei Omune, Takuma Iwaki, Kazuyuki Ueno, Mayumi Yahata, Yasufumi Ohtsuka, Eriko Nishi, Nobuya Takahashi, Tomoaki Ishikawa, Shunsuke Goto, Nobuhiko Okamoto, Kazumoto Iijima
    Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations and a 22q partial tetrasomy were identified in one family each. All patients identified with causative genes suffered from hearing loss. Second branchial arch anomalies, including a cervical fistula or cyst, preauricular pits, and renal anomalies, were frequently identified (> 60%) in patients with EYA1 aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1 aberrations. Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients.
    Nature Publishing Group, May 2018, Journal of Human Genetics, 63(5) (5), 647 - 656, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Masahiro Nishiyama, Ichiro Morioka, Mariko Taniguchi-Ikeda, Takeshi Mori, Kazumi Tomioka, Keita Nakanishi, Junya Fujimura, Noriyuki Nishimura, Kandai Nozu, Hiroaki Nagase, Kazuto Ishibashi, Akihito Ishida, Kazumoto Iijima
    Objectives To identify clinical features that predict Group A streptococcal (GAS) pharyngitis in a Japanese paediatric primary emergency medical centre. Methods The prevalence of GAS pharyngitis according to age and body temperature (BT) was calculated among 3098 paediatric patients with pharyngitis. The numbers of GAS-positive and -negative patients for each clinical parameter, and each point increase in the McIsaac score were compared and likelihood ratios (LRs) were calculated. Results The prevalence of GAS pharyngitis was extremely low in patients aged < 1 (1.2%) and 1 year (3.9%). The GAS-positive rate was significantly higher in patients with a BT < 38.0°C compared with ≥ 38.0°C (30.0% vs. 19.8%). A BT ≥ 38.0°C was not a predictive finding for GAS pharyngitis (positive LR: 0.82). Rash was the most useful individual predictor, and a McIsaac score of 4 or 5 increased the probability; however, the positive LRs were 1.74 and 1.30, respectively. Conclusions The prevalence of GAS pharyngitis is extremely low in patients aged < 1 and 1 year, and a BT ≥ 38.0°C is not a predictive symptom. Although a rash and McIsaac score of 4 or 5 are associated with an increased probability, they cannot be used to confirm GAS infection.
    May 2018, The Journal of international medical research, 46(5) (5), 1791 - 1800, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Clifford E. Kashtan, Jie Ding, Guido Garosi, Laurence Heidet, Laura Massella, Koichi Nakanishi, Kandai Nozu, Alessandra Renieri, Michelle Rheault, Fang Wang, Oliver Gross
    Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy. Herein we propose a new classification of genetic disorders of the collagen IV α345 molecule with the goal of improving renal outcomes through regular monitoring and early treatment.
    Elsevier B.V., May 2018, Kidney International, 93(5) (5), 1045 - 1051, English
    [Refereed]
    Scientific journal

  • X染色体不活化とDent病
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 貝藤 裕史, 飯島 一誠
    X染色体連鎖型腎疾患における女性症例の重症化には、X染色体不活化率の偏り(skewed X)が主な原因の一つと考えられている。X染色体不活化の解析法において、従来のHUMARA法では、i)変異遺伝子を直接測定しているものではなく、ii)ゲノムレベルの解析にとどまるという欠点があった。しかし、近年の次世代シークエンサー(NGS)の登場によりこれらの弱点を克服したRNA-Seq法による不活化解析が可能となった。Dent病は稀なX連鎖型遺伝性腎疾患であり、女性においては軽症となることが一般的であるが、一部重度の表現型を呈する症例も存在する。この原因についてはX染色体不活化の関連が疑われるが、未だそれを明確に示した報告は無く、HUMARA法やNGSを用いたX染色体不活化解析の報告が待たれる。(著者抄録)
    発達腎研究会, Apr. 2018, 発達腎研究会誌, 26(1) (1), 8 - 10, Japanese

  • X染色体連鎖型Alport症候群男性患者341名の臨床遺伝学的検討
    山村 智彦, 野津 寛大, 長野 智那, 榊原 菜々, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 貝藤 裕史, 中西 浩一, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 336 - 336, Japanese

  • Gitelman症候群185例における臨床的特徴に関する検討
    藤村 順也, 野津 寛大, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 次世代シークエンサー解析データを用いたpair解析により診断に至った遺伝性腎疾患例に関する検討
    長野 智那, 野津 寛大, 森貞 直哉, 榊原 菜々, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 多様な表現型を示したピアソン症候群における遺伝学的・分子生物学的検討
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 貝藤 裕史, 平野 大志, 原田 涼子, 濱田 陸, 西山 慶, 稲垣 徹史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 338 - 338, Japanese

  • ゲノムワイド関連解析による小児特発性ネフローゼ症候群のrisk haplotype同定
    堀之内 智子, 野津 寛大, 石倉 健司, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 344 - 344, Japanese

  • ステロイド抵抗性ネフローゼ症候群における網羅的遺伝子診断体制の構築
    中西 啓太, 野津 寛大, 榊原 菜々, 長野 智那, 藤村 順也, 堀之内 智子, 南川 将吾, 山村 智彦, 貝藤 裕史, 島 友子, 中西 浩一, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 344 - 344, Japanese

  • 抗変異MUC1抗体によるADTKD-MUC1診断の可能性
    岡田 絵里, 森貞 直哉, 森 維久郎, 山田 亜純, 上原 正樹, 岡島 真里, 川口 武彦, 首村 守俊, 北村 博司, 野津 寛大, 飯島 誠一, 今澤 俊之
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 遺伝子解析が診断に有用であったLMX1B関連腎症の1家系
    尾崎 太郎, 下野 愛子, 大西 啓右, 藤田 拓朗, 守時 政宏, 西島 陽子, 祖父江 理, 串田 吉生, 野津 寛大, 南野 哲男
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 421 - 421, Japanese

  • M. Taniguchi-Ikeda, N. Morisada, H. Inagaki, Y. Ouchi, Y. Takami, M. Tachikawa, W. Satake, K. Kobayashi, S. Tsuneishi, S. Takada, H. Yamaguchi, H. Nagase, K. Nozu, N. Okamoto, H. Nishio, T. Toda, I. Morioka, H. Wada, H. Kurahashi, K. Iijima
    Blackwell Publishing Ltd, Apr. 2018, Clinical Genetics, 93(4) (4), 931 - 933, English
    [Refereed]
    Scientific journal

  • Hiroshi Yamaguchi, Hiroaki Nagase, Yusuke Ishida, Daisaku Toyoshima, Azusa Maruyama, Kazumi Tomioka, Tsukasa Tanaka, Masahiro Nishiyama, Kyoko Fujita, Taniguchi-Ikeda Mariko, Kandai Nozu, Ichiro Morioka, Noriyuki Nishimura, Hiroshi Kurosawa, Satoshi Takada, Yoshiyuki Uetani, Kazumoto Iijima
    Several studies describing the diurnal occurrence of febrile seizures have reported greater seizure frequency early or late in the evening relative to midnight or early morning. However, no articles have reported on the diurnal occurrence of complex febrile seizure. Moreover, no studies have addressed the relationship between seizure severity and diurnal occurrence. We retrospectively evaluated complex febrile seizures in 462 children needing hospitalization, and investigated the relationship between severity and diurnal occurrence according to four categorized time periods (morning, afternoon, evening, and night). Our study showed that complex febrile seizures occurred most often in the evening, peaking around 18:00 (18:00-18:59), and least often at night (02:00-02:59). In addition, the frequency with which patients developed status epilepticus or needed anticonvulsant treatments was also lower during the night. However, the seizure duration and the proportion of the patients who needed anticonvulsant treatment were the same among the four time periods. Furthermore, we compared three subclasses (repeated episodes of convulsions, focal seizures, and prolonged seizures (≧15min)), two of the complex features (focal seizures and prolonged seizures), and all complex features among the four time periods. However, they were the same among the four time periods. Taken together, our data indicate that although the severity of seizures was stable over a 24-hour period, the occurrence of seizures in our cohort of pediatric patients with complex febrile seizures requiring hospitalization was highest in the evening and lowest at night.
    Mar. 2018, Epilepsy & behavior : E&B, 80, 280 - 284, English, International magazine
    [Refereed]
    Scientific journal

  • Fosphenytoin vs. continuous midazolam for pediatric febrile status epilepticus
    Nishiyama M, Nagase H, Tomioka K, Tanaka T, Yamaguchi H, Ishida Y, Toyoshima D, Fujita K, Maruyama A, Kurosawa H, Uetani Y, Nozu K, Taniguchi-Ikeda M, Morioka I, Takada S, Iijima K
    2018, Brain and Development, 60(8) (8), 648 - 690, English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yurika Tsuji, Kandai Nozu, Tadashi Sofue, Shigeo Hara, Keita Nakanishi, Tomohiko Yamamura, Shogo Minamikawa, Yoshimi Nozu, Hiroshi Kaito, Junya Fujimura, Tomoko Horinouchi, Naoya Morisada, Ichiro Morioka, Mariko Taniguchi-Ikeda, Masafumi Matsuo, Kazumoto Iijima
    BACKGROUND/AIMS: Glomerulopathy with fibronectin deposits (GFND; OMIM: 601894) is a very rare inherited kidney disease caused by pathogenic variants in the FN1 gene. Only 9 exonic pathogenic variants in FN1, 9 at the heparin-binding site, and 1 at the integrin-binding site have been reported. No intronic variants in FN1 have been detected. METHODS: We found a pathogenic intronic variant in intron 36 (c.5888-2A>G) located at the heparin-binding site. To determine whether this mutation influences splicing processes, we conducted RT-PCR analysis and an in vitro splicing assay using minigene construction. RESULTS: RT-PCR using RNA extracted from leukocytes of the proband failed because of the low expression of FN1 mRNA in leukocytes. We conducted in vitro functional splicing analysis using minigenes and found that c.5888-2A>G caused a 12 bp deletion at exon 37 by the activation of a novel splicing acceptor site within exon 37. We were able to detect the same abnormal transcript in mRNA extracted from the patient's urinary sediment and confirmed the pathogenicity of c.5888-2A>G by both RT-PCR using the patient sample and an in vitro splicing assay. CONCLUSION: Intronic variants can cause GFND. Minigene analysis is useful for determining the pathogenicity of the intronic variants and could be used for all inherited kidney diseases.
    2018, Nephron, 138(2) (2), 166 - 171, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Changes in the numbers of patients with acute gastroenteritis after voluntary introduction of the rotavirus vaccine in a Japanese children's primary emergency medical center
    MORIOKA Ichiro, KAMIYOSHI Naohiro, NISHIYAMA Masahiro, YAMAMURA Tomohiko, MINAMIKAWA Shogo, IWATANI Sota, NAGASE Hiroaki, NOZU Kandai, NISHIMURA Noriyuki, TANIGUCHI-IKEDA Mariko, ISHIBASHI Kazuto, ISHIDA Akihito, IIJIMA Kazumoto
    Dec. 2017, Environmental Health and Preventive Medicine (Web), 22(1) (1), 22:15 (WEB ONLY), English
    [Refereed]
    Scientific journal

  • Taketsugu Hama, Koichi Nakanishi, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Kandai Nozu, Shizuko Nagao, Hisahide Takahashi, Mayumi Sako, Kazumoto Iijima, Norishige Yoshikawa, Hiroyuki Suzuki
    Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-β/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-β, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention.
    American Physiological Society, Dec. 2017, American Journal of Physiology - Renal Physiology, 313(6) (6), F1223 - F1231, English
    [Refereed]
    Scientific journal

  • Tomoko Horinouchi, Kandai Nozu, Naohiro Kamiyoshi, Koichi Kamei, Hiroko Togawa, Yuko Shima, Yoshimichi Urahama, Tomohiko Yamamura, Shogo Minamikawa, Keita Nakanishi, Junya Fujimura, Ichiro Morioka, Takeshi Ninchoji, Hiroshi Kaito, Koichi Nakanishi, Kazumoto Iijima
    Hereditary hypomagnesemia is difficult to diagnose accurately because of its rarity and the variety of causative genes. We established a flowchart for identifying responsible genes for hypomagnesemia, and we confirmed its diagnostic efficacy in patients with suspected inherited hypomagnesemia. We established a flowchart and applied it to five index cases with suspected inherited hypomagnesemia. Direct sequence analysis was used to detect the causative gene variants in four cases, and targeted sequencing analysis using next-generation sequencing (NGS) of all causative genes for hypomagnesemia was used in one. Expected pathogenic variants were detected in the HNF1B, TRPM6, CLDN16, CASR, or SLC12A3 gene in all five cases. The results of all genetic analyses were consistent with the clinical diagnostic results using the flowchart. Accurate genetic diagnosis is crucial for estimating the prognosis, detecting complications in organs other than the kidneys, and for directing genetic counseling. The developed flowchart for identifying responsible genes for hypomagnesemia was useful for diagnosing inherited hypomagnesemia. In addition, NGS analysis will help to resolve clinical difficulties in making an accurate diagnosis and thus improve the diagnostic strategy for inherited hypomagnesemia.
    SPRINGER, Dec. 2017, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 21(6) (6), 1003 - 1010, English
    [Refereed]
    Scientific journal

  • Keita Nakanishi, Kandai Nozu, Ryugo Hiramoto, Shogo Minamikawa, Tomohiko Yamamura, Junya Fujimura, Tomoko Horinouchi, Takeshi Ninchoji, Hiroshi Kaito, Naoya Morisada, Shingo Ishimori, Koichi Nakanishi, Ichiro Morioka, Hiroyuki Awano, Masafumi Matsuo, Kazumoto Iijima
    Lowe syndrome is an X-linked inherited disorder diagnosed by congenital cataracts, intellectual impairment, and renal tubular dysfunction. It is caused by pathogenic variants of the oculocerebrorenal syndrome of Lowe gene (OCRL), of which more than 250 have been reported so far. Around 30 of these variants are intronic nucleotide changes; however, to show the pathogenicity of these variants is usually laborious. In this report, we conducted genetic testing of a patient clinically diagnosed with Lowe syndrome to detect the presence of OCRL variants. We analyzed variant transcript expression in peripheral blood leukocytes and using a minigene construct in addition to in silico analysis. We detected a 9 base pair intronic insertion between OCRL exon 10 and exon 11 derived from the alteration of the splicing acceptor site in intron 10 caused by the intronic splicing variant NM_ 000276.3: c. 940-11G> A (p. Lys313_ Val314insAsnSer*). The findings obtained from transcript analysis of peripheral blood leukocytes and the minigene construct assay were identical to those of in silico analysis. All assays detected the same transcript abnormality and were reliable in revealing the pathogenicity of the intronic variant. The in vitro assay can also be used to clarify the complicated splicing mechanisms in inherited kidney diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.
    ELSEVIER SCIENCE BV, Dec. 2017, EUROPEAN JOURNAL OF MEDICAL GENETICS, 60(12) (12), 631 - 634, English
    [Refereed]
    Scientific journal

  • Taketsugu Hama, Koichi Nakanishi, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Kandai Nozu, Shizuko Nagao, Hisahide Takahashi, Mayumi Sako, Kazumoto Iijima, Norishige Yoshikawa, Hiroyuki Suzuki
    Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-beta/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-beta/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-beta, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. alpha-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-beta/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention.
    AMER PHYSIOLOGICAL SOC, Dec. 2017, AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 313(6) (6), F1223 - F1231, English
    [Refereed]
    Scientific journal

  • Tomohiko Yamamura, Kandai Nozu, Yuya Miyoshi, Keita Nakanishi, Junya Fujimura, Tomoko Horinouchi, Shogo Minamikawa, Nobuo Mori, Rika Fujimaru, Koichi Nakanishi, Takeshi Ninchoji, Hiroshi Kaito, Taniguchi-Ikeda Mariko, Ichiro Morioka, Masafumi Matsuo, Kazumoto Iijima
    Background: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare hereditary disease caused by pathogenic variants in the ATP6V0A4 gene or ATP6V1B1 gene, and characterized by hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia and nephrocalcinosis. Although several intronic nucleotide variants in these genes have been detected, all of them fell in the apparent splice consensus sequence. In general, transcriptional analysis is necessary to determine the effect on function of the novel intronic variants located out of splicing consensus sequences. In recent years, functional splicing analysis using minigene construction was used to assess the pathogenicity of novel intoronic variant in various field.Methods: We investigated a sporadic case of dRTA with a compound heterozygous mutation in the ATP6V0A4 gene, revealed by next generation sequencing. One variant was already reported as pathogenic; however, the other was a novel variant in intron 11 (c. 1029 + 5G > A) falling outside of the apparent splicing consensus sequence. Expression of ATP6V0A4 was not detected in peripheral leukocytes by RT-PCR analysis. Therefore, an in vitro functional splicing study using minigene construction was conducted to analyze the splicing pattern of the novel variant.Results: A minigene assay revealed that the novel intronic variant leads to a 104 bp insertion immediately following exon 11. In addition, this result was confirmed using RNA extracted from the patient's cultured leukocytes.Conclusion: These results proved the pathogenicity of a novel intronic variant in our patient. We concluded that the minigene assay is a useful, non-invasive method for functional splicing analysis of inherited kidney disease, even if standard transcriptional analysis could not detect abnormal mRNA.
    BIOMED CENTRAL LTD, Dec. 2017, BMC NEPHROLOGY, 18(1) (1), 353, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Koichi Kamei, Kenji Ishikura, Mayumi Sako, Kunihiko Aya, Ryojiro Tanaka, Kandai Nozu, Hiroshi Kaito, Koichi Nakanishi, Yoshiyuki Ohtomo, Kenichiro Miura, Shori Takahashi, Tetsuji Morimoto, Wataru Kubota, Shuichi Ito, Hidefumi Nakamura, Kazumoto Iijima
    Background Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. Methods Fifty-one patients (age, 3-38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m(2) once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. Results Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) received additional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required either immunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroid toxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. Conclusions As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.
    SPRINGER, Nov. 2017, PEDIATRIC NEPHROLOGY, 32(11) (11), 2071 - 2078, English
    [Refereed]
    Scientific journal

  • Koichi Kamei, Kenji Ishikura, Mayumi Sako, Kunihiko Aya, Ryojiro Tanaka, Kandai Nozu, Hiroshi Kaito, Koichi Nakanishi, Yoshiyuki Ohtomo, Kenichiro Miura, Shori Takahashi, Tetsuji Morimoto, Wataru Kubota, Shuichi Ito, Hidefumi Nakamura, Kazumoto Iijima, on behalf of the Rituximab for Childhood-Onset Refractory Nephrotic Syndrome (RCRNS) Study Group
    Background: Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. Methods: Fifty-one patients (age, 3–38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m2 once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. Results: Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) received additional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required either immunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroid toxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. Conclusions: As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.
    Springer Verlag, Nov. 2017, Pediatric Nephrology, 32(11) (11), 2071 - 2078, English
    [Refereed]
    Scientific journal

  • Masafumi Kamijo, Mineaki Kitamura, Kumiko Muta, Tadashi Uramatsu, Yoko Obata, Kandai Nozu, Hiroshi Kaito, Kazumoto Iijima, Hiroshi Mukae, Tomoya Nishino
    In a case of 41-year-old man with mild nephropathy, Alport syndrome (AS) was diagnosed from the renal biopsy. However, the α5 chain of type IV collagen expressed in the glomerular basement membrane, which was the atypical staining pattern of AS. Genetic testing suggested autosomal recessive AS from heterozygous mutations at two positions in the type IV collagen α3 chain. These two gene mutations represented a new pattern of mutation and was suggested the association with an atypical α5 chain expression and mild phenotype.
    Nov. 2017, CEN case reports, 6(2) (2), 189 - 193, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns
    Yamana Keiji, Morioka Ichiro, Kurokawa Daisuke, Fukushima Sachiyo, Nishida Kosuke, Ohyama Shohei, Nishimura Noriyuki, Nozu Kandai, Taniguchi-Ikeda Mariko, Nagase Hiroaki, Fujioka Kazumichi, Iwatani Sota, Nakamura Hajime, Iijima Kazumoto
    Oct. 2017, Pediatrics International (Web), 59(10) (10), 1058‐1063, English
    [Refereed]
    Scientific journal

  • Kana Yokota, Kandai Nozu, Shogo Minamikawa, Tomohiko Yamamura, Keita Nakanishi, Hisashi Kaneda, Riku Hamada, Yoshimi Nozu, Akemi Shono, Takeshi Ninchoji, Naoya Morisada, Shingo Ishimori, Junya Fujimura, Tomoko Horinouchi, Hiroshi Kaito, Koichi Nakanishi, Ichiro Morioka, Mariko Taniguchi-Ikeda, Kazumoto Iijima
    X-linked Alport syndrome (XLAS) is a progressive, hereditary nephropathy. Although males with XLAS usually develop end-stage renal disease before 30 years of age, some men show a milder phenotype and possess somatic mosaic variants of the type IV collagen alpha 5 gene (COL4A5), with severity depending on variant frequencies. In females, somatic mosaic variants are rarely reported in XLAS, and it is not clear what determines severity.Two females with somatic mosaic mutations in COL4A5 with variant frequencies of 17.9 and 22.1% were detected using the next-generation sequencing. One patient only had hematuria. The other, however, had moderate proteinuria, which is a severe phenotype for a female XLAS patient of her age. The molecular mechanisms for the severe phenotype were investigated by examining variant frequencies in urinary sediment cells and X chromosome inactivation patterns, and by looking for modifier variants in podocyte-related genes using the next-generation sequencing.The severe phenotype patient had a variant frequency of 36.6% in urinary sediment cells, which is not markedly high, nor did she show skewed X chromosome inactivation. However, she did have the heterozygous variant in COL4A3, which can affect severity.Factors determining severity in female XLAS patients remain unclear. One studied patient with the somatic variant in COL4A5 showed a severe phenotype without skewed X chromosome inactivation, which might be derived from digenic variants in COL4A3 and COL4A5. Further studies are required to determine molecular mechanisms behind female XLAS resulting in the severe phenotype.
    SPRINGER, Oct. 2017, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 21(5) (5), 877 - 883, English
    [Refereed]
    Scientific journal

  • Takeshi Ninchoji, Kandai Nozu, Keita Nakanishi, Tomoko Horinouchi, Junya Fujimura, Tomohiko Yamamura, Shogo Minamikawa, Shingo Ishimori, Koichi Nakanishi, Norishige Yoshikawa, Ichiro Morioka, Hiroshi Kaito, Kazumoto Iijima
    To clarify the clinical characteristics and long-term outcomes of patients with diarrhea-associated hemolytic uremic syndrome (D + HUS) with a particular focus on time course. We retrospectively analyzed the medical records of 61 patients with D + HUS who were admitted to Kobe University Hospital between 1995 and 2015. The onset of D + HUS was defined as day 1 of diarrhea. The age of onset was 4.1 (1.5-13.4) years, and the period between onset and diagnosis of D + HUS was 5 (3-18) days. The platelet count was lowest on day 7 (4-24), and the lactase dehydrogenase level was maximal on day 8 (4-25). Twenty-three patients required dialysis for 13 (2-37) days, starting at day 5-9. Seventeen patients showed central nervous system (CNS) symptoms at day 4-18. They were followed up for 3.7 (0-18.4) years. At the final follow-up, estimated glomerular filtration rate was 113.7 (57.9-159.9) ml/min/1.73 m(2) with five patients having chronic kidney disease. Three patients developed CNS sequelae. The time to diagnosis was significantly shorter in the group of patients receiving dialysis than without dialysis (p = 0.018) and in the group with CNS complications than without (p = 0.013). CNS complications were often apparent after blood examination results improved. Moreover, a shorter period between the onset of diarrhea and a diagnosis of D + HUS indicated a more severe clinical course or long-term sequelae, and it should be considered as a risk factor for poor prognosis.
    SPRINGER, Oct. 2017, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 21(5) (5), 889 - 894, English
    [Refereed]
    Scientific journal

  • Keiji Yamana, Ichiro Morioka, Daisuke Kurokawa, Sachiyo Fukushima, Kosuke Nishida, Shohei Ohyama, Noriyuki Nishimura, Kandai Nozu, Mariko Taniguchi-Ikeda, Hiroaki Nagase, Kazumichi Fujioka, Sota Iwatani, Hajime Nakamura, Kazumoto Iijima
    BackgroundNon-invasive transcutaneous bilirubin (TcB) monitoring has been widely used to screen for hyperbilirubinemia. TcB measured using the recently developed BiliCare system, however, has not been fully evaluated.MethodsOne hundred and seven TcB measurements were obtained from 82 Japanese newborns 35 weeks' gestational age within 2 weeks after birth. Measurements were taken at the scaphoid fossa, conchal cavity, and lobe of the ear using BiliCare. BiliCare TcB were compared with total serum bilirubin (TB) and TcB obtained using another bilirubinometer (JM-105).ResultsTranscutaneous bilirubin measured at all three sites significantly correlated with TB (r = 0.91, 0.93, and 0.93 at the scaphoid fossa, conchal cavity, and lobe, respectively). The mean differences were 0.1, -0.3, and 3.6 at the scaphoid fossa, conchal cavity, and lobe, respectively. BiliCare TcB at the scaphoid fossa significantly correlated with that using the JM-105 (r = 0.91). The mean difference was 0.0. BiliCare, however, produced a significantly higher and lower TcB than the JM-105 for TB <7 and 15 mg/dL, respectively.ConclusionsTranscutaneous bilirubin measurements taken at the scaphoid fossa or conchal cavity using BiliCare were more reliable than those at the earlobe. BiliCare TcB differed from those of the JM-105, for TB <7 or 15 mg/dL.
    WILEY, Oct. 2017, PEDIATRICS INTERNATIONAL, 59(10) (10), 1058 - 1063, English
    [Refereed]
    Scientific journal

  • Miwako Nagasaka, Mariko Taniguchi-Ikeda, Hidehito Inagaki, Yuya Ouchi, Daisuke Kurokawa, Keiji Yamana, Risa Harada, Kandai Nozu, Yoshitada Sakai, Sushil K. Mishra, Yoshiki Yamaguchi, Ichiro Morioka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima
    Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c.572G> A, p.Arg191His) in the patient. DLL4 functions as a requisite ligand for NOTCH1 receptor, which is essential for vascular formation. Amino acid substitution of Arg191 to His was predicted by molecular models to interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been identified as a causative gene of an autosomal dominant type of AOS with milder symptoms. The case described here showed gradual recovery from skull defects after birth and no psychomotor developmental delay has been observed. This is the second report of an AOS case with DLL4 mutation, and the phenotypic characteristics between the two cases are compared and discussed.
    NATURE PUBLISHING GROUP, Sep. 2017, JOURNAL OF HUMAN GENETICS, 62(9) (9), 851 - 855, English
    [Refereed]
    Scientific journal

  • Miwako Nagasaka, Mariko Taniguchi-Ikeda, Hidehito Inagaki, Yuya Ouchi, Daisuke Kurokawa, Keiji Yamana, Risa Harada, Kandai Nozu, Yoshitada Sakai, Sushil K. Mishra, Yoshiki Yamaguchi, Ichiro Morioka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima
    NATURE PUBLISHING GROUP, Sep. 2017, JOURNAL OF HUMAN GENETICS, 62(9) (9), 869 - 869, English
    [Refereed]

  • Miwako Nagasaka, Mariko Taniguchi-Ikeda, Hidehito Inagaki, Yuya Ouchi, Daisuke Kurokawa, Keiji Yamana, Risa Harada, Kandai Nozu, Yoshitada Sakai, Sushil K. Mishra, Yoshiki Yamaguchi, Ichiro Morioka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima
    NATURE PUBLISHING GROUP, Sep. 2017, JOURNAL OF HUMAN GENETICS, 62(9) (9), 869 - 869, English
    [Refereed]

  • Satomi Higashi, Natsuki Matsunoshita, Masako Otani, Etsuro Tokuhiro, Kandai Nozu, Shuichi Ito
    Background: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis. Their diagnosis is frequently delayed and difficult because of slower progression to end-stage renal disease and fewer cystine crystals in the cornea. Molecular analysis and a cysteine-binding protein assay should be performed when patients with proximal tubulopathy of an unknown origin are encountered. Case presentation: A 12-year-old boy had been suffering from Fanconi syndrome since he was 3 years old. He was only recently diagnosed despite repeated ophthalmological examinations. Corneal cystine crystals were found when he was 12 years old, and he was diagnosed with cystinosis by high free cystine content in granulocytes (6.36 nmol half-cystine/mg protein, normal: < 0.15). Analysis of the CTNS gene showed two novel heterozygous single nucleotide substitutions of c.329G > C and c.329 + 2 T > C. Both were splicing site variants causing exon 6 skipping proven by transcript analysis, although the functional prediction site showed c.329G > C, p.(Gly110Ala) as a benign missense substitution. The patient's estimated glomerular filtration rate was 66.8 mL/min/1.73 m(2). He was immediately treated with cysteamine after diagnosis. Conclusions: Even if no ophthalmological abnormalities are present, nephropathic juvenile cystinosis should be suspected in children with Fanconi syndrome. Transcript analysis was useful to detect pathogenic splicing variants in this patient.
    BIOMED CENTRAL LTD, Sep. 2017, BMC NEPHROLOGY, 18(1) (1), 300, English
    [Refereed]
    Scientific journal

  • Tomohiko Yamamura, Kandai Nozu, Xue Jun Fu, Yoshimi Nozu, Ming Juan Ye, Akemi Shono, Satoko Yamanouchi, Shogo Minamikawa, Naoya Morisada, Koichi Nakanishi, Yuko Shima, Norishige Yoshikawa, Takeshi Ninchoji, Ichiro Morioka, Hiroshi Kaito, Kazumoto Iijima
    Introduction X-linked Alport syndrome (XLAS) is a hereditary disease characterized by progressive nephritis, hearing loss, and ocular abnormalities. Affected male patients usually progress to end-stage renal disease in early or middle adulthood, and disease severity is strongly correlated with genotype. However, the clinical course in female patients has rarely been reported. Methods We conducted a retrospective analysis of females with genetically proven XLAS (n = 275) and their affected female family members (n = 61) from 179 Japanese families. Patients suspected to have Alport syndrome from pathologic findings or a family history who were referred from anywhere in Japan for genetic diagnosis between 2006–2015 were included in this study. Clinical and laboratory data were collected from medical records at the time of registration for genetic analysis. Results Proteinuria was detected in 175 genetically proven patients (72.6%), and the median age for developing proteinuria was 7.0 years. Fifty-two of 336 patients developed end-stage renal disease with a median renal survival age of 65.0 years. No obvious genotype–phenotype correlation was observed. Additionally, targeted sequencing for podocyte-related genes in patients with severe phenotypes revealed no obvious variants considered to be modifier genes except for 1 patient with a COL4A3 gene variant. Discussion This study revealed that phenotypes in female XLAS patients may be severe, but genotype does not help to predict the disease severity. Clinicians must therefore pay careful attention to the clinical course and appropriate treatment in females with XLAS.
    Elsevier Inc, Sep. 2017, Kidney International Reports, 2(5) (5), 850 - 855, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kazumoto Iijima, Mayumi Sako, Koichi Kamei, Kandai Nozu
    Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80–90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10–20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS. Rituximab, a chimeric anti-CD20 monoclonal antibody that was originally developed to treat patients with B-cell non-Hodgkin’s lymphoma, is currently used for treating SSNS. In this review we highlight recent studies, mainly randomized controlled trials of rituximab for SSNS, including complicated and uncomplicated forms of FRNS or SDNS in children. We also discuss the effects of these studies on the management of patients suffering from these conditions.
    Springer Verlag, Jul. 2017, Pediatric Nephrology, 33(9) (9), 1 - 7, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kandai Nozu, Shogo Minamikawa, Shiro Yamada, Masafumi Oka, Motoko Yanagita, Naoya Morisada, Shuichiro Fujinaga, China Nagano, Yoshimitsu Gotoh, Eihiko Takahashi, Takahiro Morishita, Tomohiko Yamamura, Takeshi Ninchoji, Hiroshi Kaito, Ichiro Morioka, Koichi Nakanishi, Igor Vorechovsky, Kazumoto Iijima
    Alport syndrome-diffuse leiomyomatosis (AS-DL, OMIM: 308940) is a rare variant of the X-linked Alport syndrome that shows overgrowth of visceral smooth muscles in the gastrointestinal, respiratory and female reproductive tracts in addition to renal symptoms. AS-DL results from deletions that encompass the 5' ends of the COL4A5 and COL4A6 genes, but deletion breakpoints between COL4A5 and COL4A6 have been determined in only four cases. Here, we characterize deletion breakpoints in five AS-DL patients and show a contiguous COL4A6/COL4A5 deletion in each case. We also demonstrate that eight out of nine deletion alleles involved sequences homologous between COL4A5 and COL4A6. Most breakpoints took place in recognizable transposed elements, including long and short interspersed repeats, DNA transposons and long-terminal repeat retrotransposons. Because deletions involved the bidirectional promoter region in each case, we suggest that the occurrence of leiomyomatosis in AS-DL requires inactivation of both genes. Altogether, our study highlights the importance of homologous recombination involving multiple transposed elements for the development of this continuous gene syndrome and other atypical loss-of-function phenotypes.
    NATURE PUBLISHING GROUP, Jul. 2017, JOURNAL OF HUMAN GENETICS, 62(7) (7), 733 - 735, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Kazumoto Iijima, Toru Igarashi, Shiro Yamada, Jana Kralovicova, Yoshimi Nozu, Tomohiko Yamamura, Shogo Minamikawa, Ichiro Morioka, Takeshi Ninchoji, Hiroshi Kaito, Koichi Nakanishi, Igor Vorechovsky
    Background Disease-causing mutations that activate transposon-derived exons without creating a new splice-site consensus have been reported rarely, but they provided unique insights into our understanding of structural motifs required for inclusion of intronic sequences in mature transcripts. Methods We employ a combination of experimental and computational techniques to characterize the first de novo bipartite exon activation in genetic disease. Results The exon originated from two separate introns as a result of an in-frame COL4A5 deletion associated with a typical Alport syndrome. The deletion encompassed exons 38 through 41 and activated a cryptic 3' and 5' splice site that were derived from intron 37 and intron 41, respectively. The deletion breakpoint was in the middle of the new exon, with considerable complementarity between the two exonic parts, potentially bringing the cryptic 3' and 5' splice site into proximity. The 3' splice site, polypyrimidine tract and the branch site of the new exon were derived from an inactive, 5' truncated LINE-1 retrotransposon. This ancient LINE-1 copy sustained a series of mutations that created the highly conserved AG dinucleotide at the 3' splice site early in primate development. The exon was fully included in mature transcripts and introduced a stop codon in the shortened COL4A5 mRNA, illustrating pitfalls of inferring disease severity from DNA mutation alone. Conclusion These results expand the repertoire of mutational mechanisms that alter RNA processing in genetic disease and illustrate the extraordinary versatility of transposed elements in shaping the new exon-intron structure and the phenotypic variability.
    WILEY, May 2017, MOLECULAR GENETICS & GENOMIC MEDICINE, 5(3) (3), 287 - 294, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Mitsuhiro Okamoto, Naoki Yokoyama, Kandai Nozu, Koichi Nakanishi, Norishige Yoshikawa
    WILEY, Apr. 2017, PEDIATRICS INTERNATIONAL, 59(4) (4), 501 - 503, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Koichi Nakanishi, Masashi Sato, Taketsugu Hama, Hironobu Mukaiyama, Hiroko Togawa, Ryojiro Tanaka, Kandai Nozu, Mayumi Sako, Kazumoto Iijima, Hiroyuki Suzuki, Norishige Yoshikawa
    Despite a low incidence, nephrotic syndrome (NS) can present with IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of pediatric patients with IgAN presenting with NS (NS-IgAN) at onset have not been fully elucidated. We retrospectively analyzed 426 patients, and compared clinical and pathological (Oxford) findings between those with NS-IgAN and those with non-NS-IgAN. Among 426 patients, 30 (7.0 %) had NS-IgAN. Logistic analyses showed that male sex (OR: 7.6, p = 0.0002), M1 (OR: 10.3, p = 0.002), and E1 (OR: 15.2, p = 0.0001) were significantly related to NS. The mean observation period was 6.2 +/- 3.2 years. Although NS-IgAN was associated with significantly lower renal survival than non-NS-IgAN according to Kaplan-Meier analysis (p = 0.02), renal survival of NS-IgAN was good (92.4 % at 10 years). The most significant prognostic factor for renal survival was remission of proteinuria after treatment, and NS at onset is also a significant prognostic factor for renal survival after adjusting for remission of proteinuria. Twenty children with NS-IgAN were treated with prednisolone alone, or prednisolone and immunosuppressant. Remission of proteinuria occurred in 21 patients. Three cases of NS-IgAN progressed to stage III-V chronic kidney disease at the most recent observation. They all demonstrated heavy proteinuria after the 2-year initial treatment. The significant factor for persistent proteinuria at 5 years was S1 in NS-IgAN. The most significant factor for renal survival was responsiveness to treatment, not NS itself. As modifiable acute lesions are the dominant pathological findings in NS-IgAN, histological improvements achieved by appropriate treatments can result in a favorable prognosis.
    SPRINGER, Mar. 2017, PEDIATRIC NEPHROLOGY, 32(3) (3), 457 - 465, English
    [Refereed]
    Scientific journal

  • Tomohiko Yamamura, Naoya Morisada, Kandai Nozu, Shogo Minamikawa, Shingo Ishimori, Daisaku Toyoshima, Takeshi Ninchoji, Masato Yasui, Mariko Taniguchi-Ikeda, Ichiro Morioka, Koichi Nakanishi, Hisahide Nishio, Kazumoto Iijima
    Background Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases.Methods We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique.Results We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet-Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability.Conclusions Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.
    SPRINGER, Feb. 2017, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 21(1) (1), 136 - 142, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Yoshimi Nozu, Keita Nakanishi, Takao Konomoto, Tomoko Horinouchi, Akemi Shono, Naoya Morisada, Shogo Minamikawa, Tomohiko Yamamura, Junya Fujimura, Koichi Nakanishi, Takeshi Ninchoji, Hiroshi Kaito, Ichiro Morioka, Mariko Taniguchi-Ikeda, Igor Vorechovsky, Kazumoto Iijima
    Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy characterized by hypokalemic metabolic alkalosis with hypocalciuria and hypomagnesemia. GS clinical symptoms range from mild weakness to muscular cramps, paralysis or even sudden death as a result of cardiac arrhythmia. GS is caused by loss-of-function mutations in the solute carrier family 12 member 3 (SLC12A3) gene, but molecular mechanisms underlying such a wide range of symptoms are poorly understood. Here we report cryptic exon activation in SLC12A3 intron 12 in a clinically asymptomatic GS, resulting from an intronic mutation c. 1669+297 T>G that created a new acceptor splice site. The cryptic exon was sandwiched between the L3 transposon upstream and a mammalian interspersed repeat downstream, possibly contributing to inclusion of the cryptic exon in mature transcripts. The mutation was identified by targeted next-generation sequencing of candidate genes in GS patients with missing pathogenic SLC12A3 alleles. Taken together, this work illustrates the power of next-generation sequencing to identify causal mutations in intronic regions in asymptomatic individuals at risk of developing potentially fatal disease complications, improving clinical management of these cases.
    NATURE PUBLISHING GROUP, Feb. 2017, JOURNAL OF HUMAN GENETICS, 62(2) (2), 335 - 337, English
    [Refereed]
    Scientific journal

  • Ichiro Morioka, Naohiro Kamiyoshi, Masahiro Nishiyama, Tomohiko Yamamura, Shogo Minamikawa, Sota Iwatani, Hiroaki Nagase, Kandai Nozu, Noriyuki Nishimura, Mariko Taniguchi-Ikeda, Kazuto Ishibashi, Akihito Ishida, Kazumoto Iijima
    Background: Acute gastroenteritis (AGE) is a major reason for presentation to pediatric primary emergency medical centers. Because rotavirus vaccines were introduced in November 2011 for voluntary vaccination in Japan, we analyzed the changes in the numbers of AGE patients. Methods: The number and proportion of patients visiting Kobe children's primary emergency medical center from January 2011 to February 2015 due to AGE, out of all visiting children, were investigated retrospectively. The rotavirus and norovirus epidemic periods were defined as the periods from March to June and from November to February, respectively, based on their disease prevalence. Results: In patients <= 2 years of age, the numbers and proportions of patients with AGE were significantly decreased from 2464/14098 (17%) in 2011 to 1888/12321 (15%) in 2014 (p < 0.01). In patients <= 2 and 3-5 years of age, significant decreases in AGE patients between 2011 and 2014 were observed during the rotavirus season (from 20% [1090/5329] to 14% [642/4482] in patients aged <= 2 years and from 23% [704/3047] to 20% [572/2807] in patients aged 3-5 years, p < 0.01 and p < 0.05, respectively), but not during the norovirus season (from 19% [834/4436] to 19% [797/4160] in patients aged <= 2 years and from 20% [679/3334] to 25% [710/2852] in patients aged 3-5 years). Conclusions: The estimated rotavirus vaccine coverage in our area increased from 1% in 2011 to 49% in 2014; this coverage may have resulted in a reduction in AGE patients, both directly and indirectly, in our Japanese children's primary emergency medical center.
    SPRINGER, 2017, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 22(1) (1), 15, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hanafusa H, Morisada N, Ishida Y, Sakata R, Morita K, Miura S, Ye MJ, Yamamoto T, Okamoto N, Nozu K, Iijima K
    The 20q11.2 microdeletion is a rare chromosomal aberration characterized by intellectual disability (ID), motor developmental delay, neonatal feeding problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl with a 1.2 Mb microdeletion of 20q11.2 showed ID, motor developmental delay, and distinctive facial features without feeding problems. The deleted region was identified by array-based comparative genomic hybridization and is the smallest reported for a 20q11.2 microdeletion.
    2017, Human genome variation, 4, 17050 - 17050, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kaori Maeyama, Ichiro Morioka, Sota Iwatani, Sachiyo Fukushima, Daisuke Kurokawa, Keiji Yamana, Kosuke Nishida, Shohei Ohyama, Kazumichi Fujioka, Hiroyuki Awano, Mariko Taniguchi-Ikeda, Kandai Nozu, Hiroaki Nagase, Noriyuki Nishimura, Chika Shirai, Kazumoto Iijima
    Gestational age (GA) is thought to affect height growth in small-for-gestational age (SGA) children. However, the GA-specific trajectories in body mass index (BMI) and early appearances of adiposity rebound (AR) have not been fully investigated in a cohort of Japanese SGA children. A longitudinal cohort study was conducted with 1063 SGA children born in Kobe, Japan, with sufficient records from birth to 3 years of age. Subjects were divided into subgroups based on GA: 39-41 weeks GA (n = 723), 37-38 weeks GA (n = 256), 34-36 weeks GA (n = 62), and < 34 weeks GA (n = 22). Height and BMI were assessed at 4 months, 9 months, 1.5 years, and 3 years of age. The catch-up rate for height was GAdependent. Most children with 39-41 weeks GA (91%) caught up by 4 months of age; however, lower GA was associated with a slower elevation in the catch-up rate. The BMI trajectory during the first 3 years was also GA-dependent, with a change in GA dependency at a boundary of 37 weeks GA. Approximately 7% of SGA children had already developed AR before 3 years of age. In conclusion, growth patterns during infancy and early childhood in SGA children differ depending on GA.
    NATURE PUBLISHING GROUP, Dec. 2016, SCIENTIFIC REPORTS, 6, 38659, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ryuhei Nagao, Shinzi Suzuki, Hisashi Kawashima, Kandai Nozu, Kazumoto Iijima
    WILEY, Dec. 2016, PEDIATRICS INTERNATIONAL, 58(12) (12), 1373 - 1374, English
    [Refereed]
    Scientific journal

  • Nao Uchida, Naonori Kumagai, Kandai Nozu, Xue Jun Fu, Kazumoto Iijima, Yoshiaki Kondo, Shigeo Kure
    Alport syndrome is a progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes that encode collagen type IV alpha 3, alpha 4, and alpha 5 chains, respectively. Because of abnormal collagen chain, glomerular basement membrane becomes fragile and most of the patients progress to end-stage renal disease in early adulthood. COL4A5 mutation causes X-linked form of Alport syndrome, and two mutations in either COL4A3 or COL4A4 causes an autosomal recessive Alport syndrome. Recently, renin-angiotensin-aldosterone system (RAAS) blockade has been shown to attenuate effectively disease progression in Alport syndrome. Here we present three Japanese siblings and their father all diagnosed with autosomal recessive Alport syndrome and with different clinical courses, suggesting the importance of the early initiation of RAAS blockade. The father was diagnosed with Alport syndrome. His consanguineous parents and his wife were healthy. All three siblings showed hematuria since infancy. Genetic analysis revealed that they shared the same gene mutations in COL4A3 in a compound heterozygous state: c.2330G>A (p.Gly777A1a) from the mother and c.4354A>T (p.Ser1452Cys) from the father. Although RAAS blockade was initiated for the older sister and brother when their renal function was already impaired, it did not attenuate disease progression. In the youngest brother, RAAS blockade was initiated during normal renal function stage. After the initiation, his renal function has been normal with the very mild proteinuria to date at the age of 17 years. We propose that in Alport syndrome, RAAS blockade should be initiated earlier than renal function is impaired.
    TOHOKU UNIV MEDICAL PRESS, Nov. 2016, TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 240(3) (3), 251 - 257, English
    [Refereed]
    Scientific journal

  • Xue Jun Fu, Kandai Nozu, Aya Eguchi, Yoshimi Nozu, Naoya Morisada, Akemi Shono, Mariko Taniguchi-Ikeda, Yuko Shima, Koichi Nakanishi, Igor Vorechovsky, Kazumoto Iijima
    X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the type IV collagen alpha chain 5 gene (COL4A5). Although many COL4A5 mutations have previously been identified, pathogenic synonymous mutations have not yet been described. A family with XLAS underwent mutational analyses of COL4A5 by PCR and direct sequencing, as well as transcript analysis of potential splice site mutations. In silico analysis was also conducted to predict the disruption of splicing factor binding sites. Immunohistochemistry (IHC) of kidney biopsies was used to detect alpha 2 and alpha 5 chain expression. We identified a hemizygous point mutation, c.876A > T, in exon 15 of COL4A5 in the proband and his brother, which is predicted to result in a synonymous amino acid change, p.(Gly292Gly). Transcript analysis showed that this mutation potentially altered splicing because it disrupted the splicing factor binding site. The kidney biopsy of the proband showed lamellation of the glomerular basement membrane (GBM), while IHC revealed negative alpha 5(IV) staining in the GBM and Bowman's capsule, which is typical of XLAS. This is the first report of a synonymous COL4A5 substitution being responsible for XLAS. Our findings suggest that transcript analysis should be conducted for the future correct assessment of silent mutations.
    SPRINGER, Oct. 2016, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 20(5) (5), 699 - 702, English
    [Refereed]
    Scientific journal

  • Yoichi Iwafuchi, Tetsuo Morioka, Yuko Oyama, Kandai Nozu, Kazumoto Iijima, Ichiei Narita
    Many types of inherited renal diseases have ocular features that occasionally support a diagnosis. The following study describes an unusual example of a 40-year-old woman with granular corneal dystrophy type II complicated by renal involvement. These two conditions may coincidentally coexist however, there are some reports that demonstrate an association between renal involvement and granular corneal dystrophy type II. Granular corneal dystrophy type II is caused by a mutation in the transforming growth factor-β-induced (TGFBI) gene. The patient was referred to us because of the presence of mild proteinuria without hematuria that was subsequently suggested to be granular corneal dystrophy type II. A kidney biopsy revealed various glomerular and tubular basement membrane changes and widening of the subendothelial space of the glomerular basement membrane by electron microscopy. However, next-generation sequencing revealed that she had no mutation in a gene that is known to be associated with monogenic kidney diseases. Conversely, real-time polymerase chain reaction, using a simple buccal swab, revealed TGFBI heteromutation (R124H). The TGFBI protein plays an important role in cell-collagen signaling interactions, including extracellular matrix proteins which compose the renal basement membrane. This mutation can present not only as corneal dystrophy but also as renal disease. TGFBI-related oculorenal syndrome may have been unrecognized. It is difficult to diagnose this condition without renal electron microscopic studies. To the best of our knowledge, this is the first detailed report of nephropathy associated with a TGFBI mutation.
    S. Karger AG, Sep. 2016, Case Reports in Nephrology and Dialysis, 6(3) (3), 106 - 113, English
    [Refereed]
    Scientific journal

  • Hiromi Ohtsubo, Taro Okada, Kandai Nozu, Yutaka Takaoka, Akemi Shono, Katsuhiko Asanuma, Lifang Zhang, Koichi Nakanishi, Mariko Taniguchi-Ikeda, Hiroshi Kaito, Kazumoto Iijima, Shun-ichi Nakamura
    Glomerulopathy with fibronectin deposits (GFND) is a rare autosomal dominant disease characterized by massive fibronectin deposits, leading to end-stage renal failure. Although mutations within the heparin-binding domains of the fibronectin 1 gene (FN1) have been associated with GFND, no mutations have been reported within the integrin-binding domains.In this study, FN1 mutational analysis was conducted in 12 families with GFND. Biochemical and functional features of mutated proteins were examined using recombinant fibronectin fragments encompassing both the integrin- and heparin-binding domains.We report six FN1 mutations from 12 families with GFND, including five that are novel (p.Pro969Leu, p.Pro1472del, p.Trp1925Cys, p.Lys1953_Ile1961del, and p.Leu1974Pro). p.Pro1472del is localized in the integrin-binding domain of fibronectin, while the others are in heparin-binding domains. We detected p.Tyr973Cys, p.Pro1472del, and p.Leu1974Pro mutations in multiple families, and haplotype analysis implied that p.Pro1472del and p.Leu1974Pro are founder mutations. The protein encoded by the novel integrin-binding domain mutation p.Pro1472del showed decreased cell binding ability via the integrin-binding site. Most affected patients developed urine abnormalities during the first or second decade of life, and some mutation carriers were completely asymptomatic.This is the second large-scale analysis of GFND families and the first report of an integrin-binding domain mutation. These findings may help determine the pathogenesis of GFND.
    SPRINGER, Sep. 2016, PEDIATRIC NEPHROLOGY, 31(9) (9), 1459 - 1467, English
    [Refereed]
    Scientific journal

  • Naohiro Kamiyoshi, Kandai Nozu, Xue Jun Fu, Naoya Morisada, Yoshimi Nozu, Ming Juan Ye, Aya Imafuku, Kenichiro Miura, Tomohiko Yamamura, Shogo Minamikawa, Akemi Shono, Takeshi Ninchoji, Ichiro Morioka, Koichi Nakanishi, Norishige Yoshikawa, Hiroshi Kaito, Kazumoto Iijima
    Background and objectives Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for < 5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. Design, setting, participants, & measurements We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. Results The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. Conclusions The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes.
    AMER SOC NEPHROLOGY, Aug. 2016, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 11(8) (8), 1441 - 1449, English
    [Refereed]
    Scientific journal

  • 慢性の下痢によると考えていた低K血症に成長障害を伴いBartter症候群III型の診断に至った1例
    武市 実奈, 奥園 清香, 古野 憲司, 江藤 潤也, 都 研一, 原 寿郎, 野津 寛大
    (公社)日本小児科学会, Jul. 2016, 日本小児科学会雑誌, 120(7) (7), 1156 - 1156, Japanese
    [Refereed]

  • 異なる経過をたどった腸管出血性大腸菌による溶血性尿毒症症候群の姉妹例
    中西啓太, Minamikawa Shogo, 山村智彦, 神吉直宙, 西山将広, 忍頂寺毅史, 豊嶋大作, Nozu Kandai, 濱平陽史, Iijima Kazumoto
    Jul. 2016, 日本小児腎不全学会雑誌, 36, 175 - 178, Japanese
    [Refereed]
    Scientific journal

  • 南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 神吉 直宙, 忍頂寺 毅史, 島 友子, 中西 浩一, 服部 益治, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 93 - 93, Japanese

  • 中西 啓太, 忍頂寺 毅史, 藤村 順也, 堀之内 智子, 南川 将吾, 山村 智彦, 神吉 直宙, 石森 真吾, 野津 寛大, 森貞 直哉, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 118 - 118, Japanese

  • 山村 智彦, 野津 寛大, 中西 啓太, 堀之内 智子, 藤村 順也, 南川 将吾, 神吉 直宙, 忍頂寺 毅史, 貝藤 裕史, 森貞 直哉, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 91 - 91, Japanese

  • 神吉 直宙, 野津 寛大, 中西 啓太, 堀之内 智子, 藤村 順也, 南川 将吾, 山村 智彦, 松野下 夏樹, 忍頂寺 毅史, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 92 - 92, Japanese

  • 島 友子, 中西 浩一, 佐藤 匡, 浜 武継, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 鈴木 啓之, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 104 - 104, Japanese

  • 忍頂寺 毅史, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 南川 将吾, 山村 智彦, 神吉 直宙, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 206 - 206, Japanese

  • 高橋 弘典, 石羽澤 映美, 吉田 陽一郎, 東 寛, 藤田 裕美, 小川 弥生, 南川 将吾, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 116 - 116, Japanese

  • CAKUT及び原因不明の小児期発症慢性腎機能障害患者への包括的原因遺伝子解析
    森貞 直哉, 野津 寛大, 庄野 朱美, 忍頂寺 毅史, 叶 明娟, 井藤 奈央子, 神田 祥一郎, 亀井 宏一, 石倉 健司, 伊藤 秀一, 山本 勝輔, 里村 憲一, 服部 元史, 田中 亮二郎, 西尾 久英, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 90 - 90, Japanese
    [Refereed]

  • 24時間自由行動下血圧測定が有用であった本態性高血圧の一例
    Minamikawa Shogo, 中西啓太, 山村智彦, 神吉直宙, 忍頂寺毅史, Nozu Kandai, Iijima Kazumoto
    Jun. 2016, 日本小児高血圧研究会誌, 13(1号) (1号), 3 - 6, Japanese
    [Refereed]
    Scientific journal

  • 小児微小変化・巣状分節性糸球体硬化症の治療戦略
    飯島 一誠, 野津 寛大, 佐古 まゆみ, 中西 浩一, 吉川 徳茂
    (一社)日本腎臓学会, May 2016, 日本腎臓学会誌, 58(3) (3), 213 - 213, Japanese

  • 半月体形成性糸状体腎炎(CGN)を呈する小児IgA腎症(IgAN)の検討
    島 友子, 中西 浩一, 佐藤 匡, 向山 弘展, 浜 武継, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, May 2016, 日本腎臓学会誌, 58(3) (3), 321 - 321, Japanese

  • Takeshi Mori, Ryojiro Tanaka, Kosuke Nishida, Nobuyuki Yamamoto, Akira Hayakawa, Noriyuki Nishimura, Kandai Nozu, Kazumoto Iijima
    Transient hyperphosphatasemia (TH) is defined as marked elevation of serum alkaline phosphatase (ALP), predominantly its bone or liver isoform. It is a rare condition and is usually detected on laboratory examination in patients without any clinical symptoms. In typical patients with TH, ALP spontaneously normalizes, but no apparent cause of TH has been identified. Some drugs are suspected triggers of TH, but no clear evidence of their association with TH has been shown to date. We herein report three cases of TH in pediatric patients. Two patients were treated with cyclosporine for frequently relapsing nephrotic syndrome, and one was also taking cyclosporine for aplastic anemia. Interestingly, ALP immediately decreased after termination of cyclosporine in two patients, whereas TH lasted 4 months in the one patient who continued cyclosporine. Clearly, cyclosporine is associated with the pathophysiology of TH in children.
    WILEY-BLACKWELL, May 2016, PEDIATRICS INTERNATIONAL, 58(5) (5), 429 - 430, English
    [Refereed]
    Scientific journal

  • Naohiro Kamiyoshi, Kandai Nozu, Yoshimichi Urahama, Natsuki Matsunoshita, Tomohiko Yamamura, Shogo Minamikawa, Takeshi Ninchoji, Naoya Morisada, Koichi Nakanishi, Hiroshi Kaito, Kazumoto Iijima
    Autosomal dominant hypocalcemia type 1 (ADH1) is a relatively rare endocrine disorder characterized by hypocalcemia and inadequate parathyroid hormone secretion. ADH is caused by activating mutations in the calcium-sensing receptor (CaSR) gene, CASR. CaSR plays a crucial role in calcium and magnesium homeostasis in the kidney. ADH may be accompanied by hypokalemia and metabolic alkalosis when it is classified as type V Bartter syndrome. However, the mechanism underlying hypokalemia in this disease is unclear. We investigated a 33-year-old woman with hypocalcemia and hypoparathyroidism since childhood, whose mother also had hypocalcemia and hypoparathyroidism, but with no clinical symptoms. Blood examinations showed hypokalemia and metabolic alkalosis in the patient, but not her mother. We conducted mutation analysis and diuretic tests to clarify the patient's and her mother's diagnosis and to investigate the onset mechanism of hypokalemia in ADH1. We also determined the localization of CaSR in the kidney by immunohistochemistry. We detected a known gain-of-function mutation in CASR in both the patient and her mother. Diuretic tests revealed a response to furosemide and no reaction to thiazide in the patient, although the mother responded well to both diuretics. CaSR co-localized with the Na+-Cl- cotransporter (NCCT) on distal tubular epithelial cells. These results indicate that the NCCT in the distal convoluted tubule was secondarily affected in this patient. We conclude that the main pathogenesis of secondary hypokalemia in ADH1 in this patient was secondary NCCT dysfunction.
    SPRINGER, Apr. 2016, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 20(2) (2), 253 - 257, English
    [Refereed]
    Scientific journal

  • Mariko Taniguchi-Ikeda, Yasuhiro Takeshima, Tomoko Lee, Masahiro Nishiyama, Hiroyuki Awano, Mariko Yagi, Ai Unzaki, Kandai Nozu, Hisahide Nishio, Masafumi Matsuo, Hiroki Kurahashi, Tatsushi Toda, Ichiro Morioka, Kazumoto Iijima
    Duchene muscular dystrophy (DMD) is a progressive muscle wasting disease, caused by mutations in the dystrophin (DMD) on the X chromosome. One-third of patients are estimated to have de novo mutations. To provide in-depth genetic counseling, the comprehensive identification of mutations is mandatory. However, many DMD patients did not undergo genetic diagnosis because detailed genetic diagnosis was not available or their mutational types were difficult to identify. Here we report the genetic testing of a sporadic DMD boy, who died >20 years previously. Dried umbilical cord preserved for 38 years was the only available source of genomic DNA. Although the genomic DNA was severely degraded, multiplex ligation-dependent probe amplification analysis was performed but no gross mutations found. Sanger sequencing was attempted but not conclusive. Next-generation sequencing (NGS) was performed by controlling the tagmentation during library preparation. A nonsense mutation in DMD (p.Arg2095*) was clearly identified in the proband. Consequently, the identical mutation was detected as an 11% mosaic mutation from his healthy mother. Finally, the proband's sister was diagnosed as a non-carrier of the mutation. Thus using NGS we have identified a pathogenic DMD mutation from degraded DNA and low-level somatic mosaicism, which would have been overlooked using Sanger sequencing.
    NATURE PUBLISHING GROUP, Apr. 2016, JOURNAL OF HUMAN GENETICS, 61(4) (4), 351 - 355, English
    [Refereed]
    Scientific journal

  • Xue Jun Fu, Kandai Nozu, Hiroshi Kaito, Takeshi Ninchoji, Naoya Morisada, Koichi Nakanishi, Norishige Yoshikawa, Hiromi Ohtsubo, Natsuki Matsunoshita, Naohiro Kamiyoshi, Chieko Matsumura, Nobuaki Takagi, Kohei Maekawa, Mariko Taniguchi-Ikeda, Kazumoto Iijima
    X-linked Alport syndrome (XLAS) is a progressive, hereditary nephropathy. Although men with XLAS usually develop end-stage renal disease before 30 years of age, some men show a milder phenotype and develop end-stage renal disease later in life. However, the molecular mechanisms associated with this milder phenotype have not been fully identified. We genetically diagnosed 186 patients with suspected XLAS between January 2006 and August 2014. Genetic examination involved: (1) extraction and analysis of genomic DNA using PCR and direct sequencing using Sanger's method and (2) next-generation sequencing to detect variant allele frequencies. We identified somatic mosaic variants in the type VI collagen, alpha 5 gene (COL4A5) in four patients. Interestingly, two of these four patients with variant frequencies in kidney biopsies or urinary sediment cells of >= 50% showed hematuria and moderate proteinuria, whereas the other two with variant frequencies of <50% were asymptomatic or only had hematuria. De novo variants can occur even in asymptomatic male cases of XLAS resulting in mosaicism, with important implications for genetic counseling. This is the first study to show a tendency between the variant allele frequency and disease severity in male XLAS patients with somatic mosaic variants in COL4A5. Although this is a very rare status of somatic mosaicism, further analysis is needed to show this correlation in a larger population.
    NATURE PUBLISHING GROUP, Mar. 2016, EUROPEAN JOURNAL OF HUMAN GENETICS, 24(3) (3), 387 - 391, English
    [Refereed]
    Scientific journal

  • Daisaku Toyoshima, Naoya Morisada, Yuichi Takami, Hiroyuki Kidokoro, Masahiro Nishiyama, Taku Nakagawa, Takeshi Ninchoji, Kandai Nozu, Yasuhiro Takeshima, Satoshi Takada, Hisahide Nishio, Kazumoto Iijima
    Introduction: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is associated with paraneoplastic diseases. Because OMS can frequently relapse, patients may be inflicted with neurological problems for a long time. Recently, rituximab (RTX) was introduced as a drug to treat OMS. To assess RTX treatment, we studied a patient who experienced recurrence of OMS. Case report: A 2-year-old Japanese boy, who had left adrenal neuroblastoma, suddenly showed OMS symptoms, including ataxia and opsoclonus. Surgical resection of the tumor and subsequent steroid therapy ameliorated his symptoms. When OMS relapsed during the time when prednisolone was reduced, he was treated with full-dose RTX therapy (375 mg/m(2)/week) for 4 consecutive weeks. However, 1 year later, he presented again with OMS symptoms. This time, we only administered an additional single dose of RTX treatment (375 mg/m(2)), allowing remission of OMS symptoms. During 2 years after the additional RTX treatment, OMS symptoms did not appear, even when prednisolone was reduced. He had no adverse 'events associated with RTX during the whole treatment period. Conclusions: An additional single-dose RTX therapy might be effective for relapsed OMS patients who were previously treated with full-dose RTX therapy. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
    ELSEVIER SCIENCE BV, Mar. 2016, BRAIN & DEVELOPMENT, 38(3) (3), 346 - 349, English
    [Refereed]
    Scientific journal

  • 次世代シークエンサーによる常染色体優性Alport症候群診断法の確立
    神吉 直宙, 野津 寛大, 中西 啓太, 堀之内 智子, 藤村 順也, 南川 将吾, 山村 智彦, 松野下 夏樹, 忍頂寺 毅史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2016, 日本小児科学会雑誌, 120(2) (2), 240 - 240, Japanese

  • 腎移植後にウイルス関連の重症合併症を呈した4症例
    南川 将吾, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 神吉 直宙, 忍頂寺 毅史, 野津 寛大, 早川 晶, 飯島 一誠
    (公社)日本小児科学会, Feb. 2016, 日本小児科学会雑誌, 120(2) (2), 242 - 242, Japanese

  • Natsuki Matsunoshita, Kandai Nozu, Akemi Shono, Yoshimi Nozu, Xue Jun Fu, Naoya Morisada, Naohiro Kamiyoshi, Hiromi Ohtsubo, Takeshi Ninchoji, Shogo Minamikawa, Tomohiko Yamamura, Koichi Nakanishi, Norishige Yoshikawa, Yuko Shima, Hiroshi Kaito, Kazumoto Iijima
    Purpose: Phenotypic overlap exists among type III Bartter syndrome (BS), Gitelman syndrome (GS), and pseudo-BS/GS -(p-BS/GS), which are clinically difficult to distinguish. We aimed to clarify the differences between these diseases, allowing accurate diagnosis based on their clinical features. Methods: A total of 163 patients with genetically defined type III BS (n = 30), GS (n = 90), and p-BS/GS (n = 43) were included. Age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations were determined. Results: Patients with p-BS/GS were significantly older at diagnosis than those with type III BS and GS. Patients with p-BS/GS included a significantly higher percentage of women and had a lower body mass index and estimated glomerular filtration rate than did patients with GS. Although hypomagnesemia and hypocalciuria were predominant biochemical findings in patients with GS, 17 and 23% of patients with type III BS and p-BS/GS, respectively, also showed these abnormalities. Of patients with type III BS, GS, and p-BS/GS, 40, 12, and 63%, respectively, presented with chronic kidney disease. Conclusions: This study clarified the clinical differences between BS, GS, and p-BS/GS for the first time, which will help clinicians establish differential diagnoses for these three conditions.
    NATURE PUBLISHING GROUP, Feb. 2016, GENETICS IN MEDICINE, 18(2) (2), 180 - 188, English
    [Refereed]
    Scientific journal

  • Masashi Nishida, Fusako Hashimoto, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Dai Asada, Kenji Hamaoka
    To date, there have been a very limited number of case reports on combined Alport syndrome (AS) and Klinefelter syndrome (KS). We herein describe the case of a 9-month-old boy diagnosed with concomitant AS and KS. KS was detected on chromosomal analysis of the amniotic fluid, and hematuria/proteinuria was identified in urinary screening at 6months of age. Renal biopsy indicated AS, with complete deficit of the 5 chain of type IV collagen in the glomerular basement membranes. On genetic analysis for AS, de novo homozygote mutation (c.3605-2a > c) was seen in the gene encoding 5 chain of type IV collagen (COL4A5) on the X chromosomes of maternal origin. This is the first case report of combined AS and KS diagnosed during infancy, and it indicates the need to consider the concurrent existence of these two disorders in infants with urine abnormalities, even in the absence of a family history.
    WILEY-BLACKWELL, Feb. 2016, PEDIATRICS INTERNATIONAL, 58(2) (2), 152 - 155, English
    [Refereed]
    Scientific journal

  • 李知子, 松野下夏樹, 野津寛大, 水戸守寿洋, Iijima Kazumoto, 竹島泰弘
    生後2ヵ月、男児。発熱と体重増加不良を主訴に近医を受診、高ナトリウム血症、低張尿を指摘され、精査加療目的で著者らの施設へ入院となった。所見ではCRPの上昇や、尿所見、胸部Xpからの尿路感染症、または肺炎は否定的であった。しかし、著明な血漿浸透圧の上昇を認めるのに対し、尿浸透圧が低値であることから尿崩症が示唆され、更にその後の精査により、本症例はAVPR2遺伝子変異の先天性腎性尿崩症の診断に至った。以後、サイアザイド系利尿薬の内服を開始し、白湯などによる水補給の指導を行ったところ、速やかに高ナトリウム血症は改善し、かつ身長、体重の発育も徐々に改善傾向を示した。
    (一社)西宮市医師会, 2016, 西宮市医師会医学雑誌, 21(21) (21), 44 - 47, Japanese
    [Refereed]
    Scientific journal

  • Yoshifusa Abe, Masayuki Iyoda, Kandai Nozu, Satoshi Hibino, Kei Hihara, Yutaka Yamaguchi, Tomohiko Yamamura, Shogo Minamikawa, Kazumoto Iijima, Takanori Shibata, Kazuo Itabashi
    We herein report a novel mutation in a Japanese family with an X-linked Alport syndrome (AS) mutation in COL4A5. Patient 1 was a 2-year-old Japanese girl. She and her mother (patient 2) had a history of proteinuria and hematuria without renal dysfunction, deafness, or ocular abnormalities. Pathological findings were consistent with AS, and a genetic analysis revealed that both patients had a heterozygous mutation (c.2767G> C) in exon 32. In summary, the identification of mutations and characteristic pathological findings was useful in making a diagnosis of AS. For a close long-term follow-up, the early detection and treatment of women with X-linked AS are important.
    JAPAN SOC INTERNAL MEDICINE, 2016, INTERNAL MEDICINE, 55(19) (19), 2843 - 2847, English
    [Refereed]
    Scientific journal

  • Asumi Higa, Yuko Shima, Taketsugu Hama, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Ryojiro Tanaka, Kandai Nozu, Mayumi Sako, Kazumoto Iijima, Koichi Nakanishi, Norishige Yoshikawa
    Some patients with childhood immunoglobulin A nephropathy (IgAN) progress to end-stage renal disease within 20 years, while others achieve spontaneous remission even without medication. Prognosis of IgAN with minimal proteinuria (MP-IgAN, < 0.5 g/day/1.73 m(2)) at diagnosis seems to be generally good. However, the long-term outcome for patients with childhood MP-IgAN has not yet been determined. We retrospectively analyzed 385 children newly diagnosed with biopsy-proven IgAN between June 1976 and July 2009 whose renal biopsy specimens could be evaluated by the Oxford classification criteria. Of these 385 children with IgAN, 106 (27.5 %) were diagnosed with MP-IgAN. We compared clinical and pathological findings between the 106 patients with MP-IgAN and the remaining 279 patients to elucidate the characteristics of MP-IgAN in children. Patients with MP-IgAN were identified through a school screening program (73.6 %) or upon presentation with gross hematuria (26.4 %). Patients with MP-IgAN had significantly milder pathological symptoms than those with IgAN. The most frequently used therapeutic regimes were angiotensin converting enzyme inhibitors (30.2 %) and no therapy (36.8 %). None of the patients with MP-IgAN reached stage III chronic kidney disease within 15 years after onset. Four patients with MP-IgAN (3.8 %) received immunosuppressive therapy during the course of the disease. Our results indicate that the outcome of patients with a diagnosis of childhood MP-IgAN is good, but that careful long-term observation is required.
    SPRINGER, Dec. 2015, PEDIATRIC NEPHROLOGY, 30(12) (12), 2121 - 2127, English
    [Refereed]
    Scientific journal

  • 島 友子, 中西 浩一, 濱 武継, 佐藤 匡, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Nov. 2015, 日本小児腎臓病学会雑誌, 28(2) (2), 177 - 177, Japanese

  • Tomoko Horinouchi, Kandai Nozu, Kiyoshi Hamahira, Yosuke Inaguma, Jun Abe, Hiroshi Nakajima, Masaaki Kugo, Kazumoto Iijima
    Background: The etiology of Kawasaki disease (KD) is unknown. Reportedly, there is an association between KD and Yersinia pseudotuberculosis (YPT). Steroid therapy for KD patients with high risk of cardiac sequelae (CS) has been reported; however, the number of reports is limited. Methods: We conducted a prospective study of 108 patients with newly diagnosed KD in one year to determine how many KD patients have positive anti-YPT antibody titers and/or positive anti-YPT-derived mitogen (YPM) antibody titers. In addition, we tried to identify clinical differences between KD patients in whom YPT infection was or not a contributing factor. We also compared clinical characteristics of patients treated with the protocol of the Randomized controlled trial to Assess Immunoglobulin plus Steroid Efficacy for Kawasaki disease (RAISE) study (RAISE group) and with the conventional Intravenous immunoglobulin (IVIG) protocol (conventional group). Results: Eleven patients (10 %) were positive for anti-YPT and/or anti-YPM antibodies (positive group) and 97 (90 %) were negative (negative group). Cardiac sequelae (CS) occurred significantly more frequently in the positive than the negative group (two patients, 18 % vs one patient, 1 %, p = 0.027). Forty patients were in the RAISE group. Two of 40 (5 %) in the RAISE group and one of 68 (1.47 %) in the conventional group had CS (p = 0.55). Conclusions: KD patients with YPT infection had CS significantly more frequently and treatment with RAISE protocol did not decrease the frequency of CS in our cohort, nor did YPT infection affect risk scores of no response to IVIG. However, our sample size was overly small to draw such conclusions. Further investigation in a larger cohort is necessary to confirm our findings. Additionally, further research is needed to determine whether early diagnosis of YPT can prevent KD from developing and reduce the incidence of CS.
    BIOMED CENTRAL LTD, Nov. 2015, BMC Pediatrics, 15, 177, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hisamatsu Chieko, MaedaK, AidaY, YasufukuM, Ninchoji Takeshi, KaitoH, Nozu Kandai, Iijima Kazumoto, NishijimaE
    Oct. 2015, J Pediatr Urol, 11(5) (5), 299 - 300, English
    [Refereed]
    Scientific journal

  • Takeshi Kato, Naoya Morisada, Hiroaki Nagase, Masahiro Nishiyama, Daisaku Toyoshima, Taku Nakagawa, Azusa Maruyama, Xue Jun Fu, Kandai Nozu, Hiroko Wada, Satoshi Takada, Kazumoto Iijima
    Introduction: CDKL5-related encephalopathy is an. X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes. Methods: We conducted a genetic analysis using an Illumina (R) TruSight (TM) One sequencing panel on a next-generation sequencer. Results: We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boy's karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal. seizures-1, and this variant showed paternal inheritance. Conclusions: Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
    ELSEVIER SCIENCE BV, Oct. 2015, BRAIN & DEVELOPMENT, 37(9) (9), 911 - 915, English
    [Refereed]
    Scientific journal

  • Noriko Miyake, Hiroyasu Tsukaguchi, Eriko Koshimizu, Akemi Shono, Satoko Matsunaga, Masaaki Shiina, Yasuhiro Mimura, Shintaro Imamura, Tomonori Hirose, Koji Okudela, Kandai Nozu, Yuko Akioka, Motoshi Hattori, Norishige Yoshikawa, Akiko Kitamura, Hae Il Cheong, Shoji Kagami, Michiaki Yamashita, Atsushi Fujita, Satoko Miyatake, Yoshinori Tsurusaki, Mitsuko Nakashima, Hirotomo Saitsu, Kenichi. Ohashi, Naoko Imamoto, Akihide Ryo, Kazuhiro Ogata, Kazumoto Iijima, Naomichi Matsumoto
    The nuclear pore complex (NPC) is a huge protein complex embedded in the nuclear envelope. It has central functions in nucleocytoplasmic transport, nuclear framework, and gene regulation. Nucleoporin 107 kDa (NUP107) is a component of the NPC central scaffold and is an essential protein in all eukaryotic cells. Here, we report on biallelic NUP107 mutations in nine affected individuals who are from five unrelated families and show early-onset steroid-resistant nephrotic syndrome (SRN). These individuals have pathologically focal segmental glomerulosclerosis, a condition that leads to end-stage renal disease with high frequency. NUP107 is ubiquitously expressed, including in glomerular podocytes. Three of four NUP107 mutations detected in the affected individuals hamper NUP107 binding to NUP133 (nucleoporin 133 kDa) and NUP107 incorporation into NPCs in vitro. Zebrafish with nup107 knockdown generated by morpholino oligonucleotides displayed hypoplastic glomerulus structures and abnormal podocyte foot processes, thereby mimicking the pathological changes seen in the kidneys of the SRNS individuals with NUP107 mutations. Considering the unique properties of the podocyte (highly differentiated foot-process architecture and slit membrane and the inability to regenerate), we propose a "podocyte-injury model" as the pathomechanism for SRNS due to biallelic NUP107 mutations.
    CELL PRESS, Oct. 2015, AMERICAN JOURNAL OF HUMAN GENETICS, 97(4) (4), 555 - 566, English
    [Refereed]
    Scientific journal

  • Chieko Hisamatsu, Kosaku Maeda, Yosuke Aida, Masao Yasufuku, Takeshi Ninchoji, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Eiji Nishijima
    Objective Pericatheter leakage is a catheter-related complication of peritoneal dialysis (PD). To prevent pericatheter leakage, a modified technique of PD catheter insertion with fibrin glue was performed in 19 children. Methods At the time of PD catheter insertion, as much fibrin glue as possible was injected into the subcutaneous tissue along the tunneled segment of the catheter and then the skin was compressed. Results There was no occurrence of pericatheter leakage and full PD could be initiated 1 day (median) after implantation. Conclusions This technique prevented pericatheter leakage completely even in smaller-weight infants and will enable initiation of full PD with no break-in period.
    ELSEVIER SCI LTD, Oct. 2015, JOURNAL OF PEDIATRIC UROLOGY, 11(5) (5), 299 - 300, English
    [Refereed]
    Scientific journal

  • 発症時ネフローゼ症候群を呈する小児IgA腎症(NS-IgAN)の検討
    島 友子, 中西 浩一, 濱 武継, 佐藤 匡, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 92 - 92, Japanese

  • びまん性メサンギウム細胞増殖を呈した特発性ネフローゼ症候群の臨床病理学的検討
    山村 智彦, 忍頂寺 毅史, 南川 将吾, 神吉 直宙, 松野下 夏樹, 大坪 裕美, 野津 寛大, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 146 - 146, Japanese

  • 初回腎生検でIgA陽性だったが二回目に陰性化していたAlport症候群の一男児例
    橋本 多恵子, 荻野 大助, 三井 哲夫, 松永 明, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 219 - 219, Japanese

  • 初診時高血圧を呈さず特発性ネフローゼ症候群との鑑別を要した腎血管性高血圧の1例
    Ninchoji Takeshi, 南川将吾, 神吉直宙, 松野下夏樹, 大坪裕美, 貝藤裕史, 野津寛大, Iijima Kazumoto
    Jun. 2015, 日本小児高血圧研究会誌, 12(1号) (1号), 31 - 35, Japanese
    [Invited]
    Research institution

  • Koichi Kamei, Koichi Nakanishi, Shuichi Ito, Kenji Ishikura, Hiroshi Hataya, Masataka Honda, Kandai Nozu, Kazumoto Iijima, Yuko Shima, Norishige Yoshikawa
    Although a 2-year combination therapy is effective for severe childhood immunoglobulin A (IgA) nephropathy, proteinuria persists in some patients even after the treatment. Seventy-nine patients aged < 18 years with IgA nephropathy in which > 80 % of glomeruli showed mesangial proliferation were enrolled in the study. Risk factors for persistent proteinuria after combination therapy were investigated using multivariate logistic regression analysis. Proteinuria (a parts per thousand yen0.2 g/1.73 m(2)/day) persisted in 27 patients (34 %) after the combination therapy. Twenty-four-hour urinary protein excretion, rate of glomeruli with crescents, rate of glomeruli with segmental sclerosis and rate of glomeruli with global sclerosis at diagnosis were higher in patients with persistent proteinuria than those without. In the multivariate analysis, 24-h urinary protein excretion [odds ratio (OR) 6.9; 95 % confidence interval (CI) 2.1-27.8; p = 0.001] and rate of glomeruli with crescents (OR 3.8; 95 % CI 1.1-13.9; p = 0.03) were independent risk factors for persistent proteinuria. Analysis of the receiver operating characteristic curve demonstrated that the most accurate cut-off values to detect persistent proteinuria were a urinary protein excretion of 1.32 g/1.73 m(2)/day and a 14 % rate of glomeruli with crescents. In our cohort, urinary protein excretion and rate of glomeruli with crescents at diagnosis were independent risk factors for persistent proteinuria after the combination therapy.
    SPRINGER, Jun. 2015, PEDIATRIC NEPHROLOGY, 30(6) (6), 961 - 967, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, William E. Sweeney, Ellis D. Avner
    Future Medicine Ltd., Mar. 2015, Polycystic Kidney Disease: From Bench to Bedside, 43 - 58, English
    [Refereed]
    In book

  • Taketsugu Hama, Koichi Nakanishi, Yuko Shima, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Kiyoshi Hamahira, Ryojiro Tanaka, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa
    The criterion for performing a renal biopsy in children with idiopathic nephrotic syndrome (NS) showing microscopic hematuria at onset remains controversial. To determine an adequate renal biopsy criterion in children with NS showing hematuria, the optimal cutoff for the maximum red blood cell (RBC) range in urine sediment to separate minimal change disease (MCD) from other glomerular changes was obtained by receiver operating characteristic analysis. We studied 29 children with NS showing hematuria who were screened from 1,320 patients who underwent renal biopsies between January 2001 and September 2011. Patients were divided into two groups according to the cutoff value to verify its validity. The optimal maximum RBC range was 30-49/high-power field (HPF). In group 1 (RBC a parts per thousand currency sign29/HPF, n = 14), 3 patients showed nephritis and the other 11 patients showed MCD. In group 2 (RBC a parts per thousand yen30/HPF, n = 15), 1 patient showed focal segmental glomerulosclerosis, 12 showed nephritis, and the other 2 showed MCD. These findings indicated that the ratio of non-MCD/MCD was significantly higher in group 2 than in group 1 (P < 0.01). The use of maximum RBC range (30-49/HPF) for a criterion of renal biopsy in patients with NS showing hematuria may be reasonable for clinical practice.
    SPRINGER, Mar. 2015, PEDIATRIC NEPHROLOGY, 30(3) (3), 445 - 450, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Koichi Nakanishi, Taketsugu Hama, Masashi Sato, Hironobu Mukaiyama, Hiroko Togawa, Ryojiro Tanaka, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa
    Although the Oxford classification of IgA nephropathy appears valid, we found crescents were significantly related to renal outcome in our cohort, whereas segmental glomerulosclerosis (S) was not. The timing of renal biopsy may significantly affect the variables in the Oxford classification. The relationship between biopsy timing and pathological variables (mesangial hypercellularity score [M], endocapillary hypercellularity [E], S, tubular atrophy/interstitial fibrosis [T], crescents, and global glomerulosclerosis [G]) was analyzed retrospectively in 250 children with IgA nephropathy. The median time from disease onset to renal biopsy was 5.1 months (interquartile range, 2.7-15.4). M (rho = -0.26, P < 0.0001), E (rho = -0.34, P < 0.0001), and crescents (rho = -0.14, P = 0.023) showed significant negative correlations, and S (rho = 0.15, P = 0.018) and G (rho = 0.25, P < 0.0001) showed significant positive correlations with time to biopsy (Spearman test). M, E, and crescents differed significantly in renal biopsies obtained before and after 3 years from onset (Wilcoxon test). Most crescents (92.9 %) were cellular/fibrocellular and were acute lesions. As crescents formed early after disease onset and decreased over time, they may be prognostic for acute phase, but not for chronic phase disease. Renal biopsy timing may alter the significance of variables used in the Oxford classification.
    SPRINGER, Feb. 2015, PEDIATRIC NEPHROLOGY, 30(2) (2), 293 - 299, English
    [Refereed]
    Scientific journal

  • [Bartter syndrome and Gitelman syndrome].
    Matsunoshita N, Nozu K, Iijima K
    日本腎臓学会, 2015, Nihon Jinzo Gakkai shi, 57(4) (4), 743 - 750, Japanese
    [Refereed]

  • Iijima Kazumoto, SakoM, Nozu Kandai
    2015, Curr Pediatr Rep, 3(1) (1), 71 - 77, English
    [Refereed]
    Scientific journal

  • Kazumoto Iijima, Mayumi Sako, Kandai Nozu, Hidefumi Nakamura, Shuichi Ito
    ELSEVIER SCIENCE INC, Jan. 2015, LANCET, 385(9964) (9964), 226 - 227, English
    [Refereed]
    Scientific journal

  • Norishige Yoshikawa, Koichi Nakanishi, Mayumi Sako, Mari S. Oba, Rintaro Mori, Erika Ota, Kenji Ishikura, Hiroshi Hataya, Masataka Honda, Shuichi Ito, Yuko Shima, Hiroshi Kaito, Kandai Nozu, Hidefumi Nakamura, Takashi Igarashi, Yasuo Ohashi, Kazumoto Iijima
    In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome.
    NATURE PUBLISHING GROUP, Jan. 2015, KIDNEY INTERNATIONAL, 87(1) (1), 225 - 232, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Igor Vorechoysky, Hiroshi Kaito, Xue Jun Fu, Koichi Nakanishi, Yuya Hashimura, Fusako Hashimoto, Koichi Kamei, Shuichi Ito, Yoshitsugu Kaku, Toshiyuki Imasawa, Katsumi Ushijima, Junya Shimizu, Yoshio Makita, Takao Konomoto, Norishige Yoshikawa, Kazumoto Iijima
    Background and objectives X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. Design, setting, participants, & measurements In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) mRNA analysis using RT-PCR to detect RNA processing abnormalities. Results Six splicing consensus site mutations resulting in aberrant splicing patterns, one exonic mutation leading to exon skipping, and four deep intronic mutations producing cryptic splice site activation were identified. Interestingly, one case produced a cryptic splice site with a single nucleotide substitution in the deep intron that led to intronic exonization containing a stop codon; however, the patient showed a clearly milder phenotype for X-linked Alport syndrome in men with a truncating mutation. mRNA extracted from the kidney showed both normal and abnormal transcripts, with the normal transcript resulting in the milder phenotype. This novel mechanism leads to mild clinical characteristics. Conclusions This report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked Alport syndrome.
    AMER SOC NEPHROLOGY, Nov. 2014, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 9(11) (11), 1958 - 1964, English
    [Refereed]
    Scientific journal

  • ストレス時に増悪する低K血症で発見されたGitelman症候群の姉弟例
    稲冨 淳, 松島 悟, 三谷 友一, 八鍬 瑛子, 太田 英仁, 中釜 悠, 増井 礼子, 柳澤 敦広, 野津 寛大, 松野下 夏樹, 飯島 一誠
    (公社)日本小児科学会, Oct. 2014, 日本小児科学会雑誌, 118(10) (10), 1553 - 1553, Japanese
    [Refereed]

  • Kazumoto Iijima, Mayumi Sako, Kandai Nozu, Rintaro Mori, Nao Tuchida, Koichi Kamei, Kenichiro Miura, Kunihiko Aya, Koichi Nakanishi, Yoshiyuki Ohtomo, Shori Takahashi, Ryojiro Tanaka, Hiroshi Kaito, Hidefumi Nakamura, Kenji Ishikura, Shuichi Ito, Yasuo Ohashi
    Background Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. Methods We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Findings Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0.27, 0.14-0.53; p < 0.0001). Ten patients (42%) in the rituximab group and six (25%) in the placebo group had at least one serious adverse event (p = 0.36). Interpretation Rituximab is an effective and safe treatment for childhood-onset, complicated FRNS and SDNS.
    ELSEVIER SCIENCE INC, Oct. 2014, LANCET, 384(9950) (9950), 1273 - 1281, English
    [Refereed]
    Scientific journal

  • Naoya Morisada, Takashi Sekine, Shingo Ishimori, Masahiko Tsuda, Masao Adachi, Kandai Nozu, Koichi Nakanishi, Ryojiro Tanaka, Kazumoto Iijima
    Microdeletion of 16q12 is a rare chromosomal abnormality. We present the cases of two Japanese patients with developmental and renal symptoms of differing clinical severity. Both patients had 16q12 interstitial microdeletions that included the entire SALL1 gene. Patient 1 was a 15-year-old Japanese boy clinically diagnosed with branchio-oto-renal syndrome with mild developmental delay, but with no imperforate anus or polydactyly. Array comparative genome hybridization (aCGH) indicated a 5.2Mb deletion in 16q12, which included SALL1. Patient 2 was a 13-year-old Japanese boy diagnosed with Townes-Brocks syndrome and severe developmental delay, epilepsy, and renal insufficiency requiring renal replacement therapy. Fluorescence in situ hybridization indicated deletion of the entire SALL1 gene. Subsequent aCGH showed a 6Mb deletion in 16q12q13, which included SALL1. Precise analysis of the present two cases will give us some clues to elucidate the pathogenic mechanisms of 16q12 microdeletion syndrome.
    WILEY-BLACKWELL, Oct. 2014, PEDIATRICS INTERNATIONAL, 56(5) (5), E75 - E78, English
    [Refereed]
    Scientific journal

  • Oka M, Nozu Kandai, Kaito Hiroshi, Fu XJ, Nakanishi K, Hashimura Y, Morisada Naoya, Yan K, Matsuo M, Yoshikawa N, Vorechovsky I, Iijima Kazumoto
    BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is a rare hereditary disease caused by homozygous or compound heterozygous mutations in either the COL4A3 or COL4A4 genes. Failure to diagnose ARAS cases is common, even if detailed clinical and pathological examinations are carried out. As the mutation detection rate for ARAS is unsatisfactory, we sought to develop more reliable diagnostic methods and provide a better description of the clinicopathological characteristics of this disorder. METHODS: A retrospective analysis of 30 genetically diagnosed patients with ARAS in 24 pedigrees was conducted. The mutation detection strategy comprised three steps: (1) genomic DNA analysis using polymerase chain reaction (PCR) and direct sequencing; (2) mRNA analysis using reverse transcription (RT)-PCR to detect RNA processing abnormalities; (3) semi-quantitative PCR using capillary electrophoresis to detect large heterozygous deletions. RESULTS: Using the three-step analysis, we identified homozygous or compound heterozygous mutations in all patients. Interestingly, 20% of our ARAS patients showed normal expression of α5 in kidney tissue. The median age of developing end-stage renal disease was 21 years. CONCLUSIONS: The strategy described in this study improves the diagnosis for ARAS families. Although immunohistochemical analysis of α5 can provide diagnostic information, normal distribution does not exclude the diagnosis of ARAS.
    Sep. 2014, Pediatr Nephrol, 29(9) (9), 1535 - 1544, English, International magazine
    [Refereed]
    Scientific journal

  • Masafumi Oka, Kandai Nozu, Hiroshi Kaito, Xue Jun Fu, Koichi Nakanishi, Yuya Hashimura, Naoya Morisada, Kunimasa Yan, Masafumi Matsuo, Norishige Yoshikawa, Igor Vorechovsky, Kazumoto Iijima
    Autosomal recessive Alport syndrome (ARAS) is a rare hereditary disease caused by homozygous or compound heterozygous mutations in either the COL4A3 or COL4A4 genes. Failure to diagnose ARAS cases is common, even if detailed clinical and pathological examinations are carried out. As the mutation detection rate for ARAS is unsatisfactory, we sought to develop more reliable diagnostic methods and provide a better description of the clinicopathological characteristics of this disorder. A retrospective analysis of 30 genetically diagnosed patients with ARAS in 24 pedigrees was conducted. The mutation detection strategy comprised three steps: (1) genomic DNA analysis using polymerase chain reaction (PCR) and direct sequencing; (2) mRNA analysis using reverse transcription (RT)-PCR to detect RNA processing abnormalities; (3) semi-quantitative PCR using capillary electrophoresis to detect large heterozygous deletions. Using the three-step analysis, we identified homozygous or compound heterozygous mutations in all patients. Interestingly, 20 % of our ARAS patients showed normal expression of alpha 5 in kidney tissue. The median age of developing end-stage renal disease was 21 years. The strategy described in this study improves the diagnosis for ARAS families. Although immunohistochemical analysis of alpha 5 can provide diagnostic information, normal distribution does not exclude the diagnosis of ARAS.
    SPRINGER, Sep. 2014, PEDIATRIC NEPHROLOGY, 29(9) (9), 1535 - 1544, English
    [Refereed]
    Scientific journal

  • Nozu Kandai, Iijima Kazumoto, Ohtsuka Y, Fu XJ, Kaito Hiroshi, Nakanishi K, Vorechovsky I
    Sep. 2014, Mol Genet Genomic Med, 2(5) (5), 451 - 3, English
    [Refereed]
    Scientific journal

  • Naoya Morisada, Kandai Nozu, Kazumoto Iijima
    Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchiogenic malformation, hearing loss and renal anomalies. The prevalence of BOR syndrome is 1/40000 in Western countries, and nationwide surveillance in 2009-2010 identified approximately 250 BOR patients in Japan. Three causative genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the causative genes for approximately half of all BOR patients remain unknown. This review article discusses the epidemiology, clinical symptoms, genetic background and management of BOR syndrome.
    WILEY-BLACKWELL, Jun. 2014, PEDIATRICS INTERNATIONAL, 56(3) (3), 309 - 314, English
    [Refereed]
    Scientific journal

  • Yuya Hashimura, Kandai Nozu, Hiroshi Kaito, Koichi Nakanishi, Xue Jun Fu, Hiromi Ohtsubo, Fusako Hashimoto, Masafumi Oka, Takeshi Ninchoji, Shingo Ishimori, Naoya Morisada, Natsuki Matsunoshita, Naohiro Kamiyoshi, Norishige Yoshikawa, Kazumoto Iijima
    X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen alpha 5 chain (alpha 5(IV)). Complete absence of alpha 5(IV) in the renal basal membrane is considered a pathological characteristic in male patients; however, positive alpha 5(IV) staining has been found in over 20% of patients. We retrospectively studied 52 genetically diagnosed male X-linked Alport syndrome patients to evaluate differences in clinical characteristics and renal outcomes between 15 alpha 5(IV)-positive and 37 alpha 5(IV)-negative patients. Thirteen patients in the alpha 5(IV)-positive group had non-truncating mutations consisting of nine missense mutations, three in-frame deletions, and one splice-site mutation resulting in small in-frame deletions of transcripts. The remaining two showed somatic mutations with mosaicism. Missense mutations in the alpha 5(IV)-positive group were more likely to be located before exon 25 compared with missense mutations in the alpha 5(IV)-negative group. Furthermore, urinary protein levels were significantly lower and the age at onset of end-stage renal disease was significantly higher in the positive group than in the negative group. These results help to clarify the milder clinical manifestations and molecular characteristics of male X-linked Alport syndrome patients expressing the alpha 5(IV) chain.
    NATURE PUBLISHING GROUP, May 2014, KIDNEY INTERNATIONAL, 85(5) (5), 1208 - 1213, English
    [Refereed]
    Scientific journal

  • 比嘉 明日美, 島 友子, 浜 武継, 佐藤 匡, 向山 弘展, 戸川 寛子, 田中 亮二郎, 貝藤 裕史, 野津 寛大, 飯島 一誠, 中西 浩一, 吉川 徳茂
    (一社)日本小児腎臓病学会, Apr. 2014, 日本小児腎臓病学会雑誌, 27(1Suppl.) (1Suppl.), 111 - 111, Japanese

  • 鈴木 慎二, 長尾 竜兵, 赤羽 麻衣, 千代反田 雅子, 三浦 太郎, 熊田 篤, 柏木 保代, 河島 尚志, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2014, 日本小児腎臓病学会雑誌, 27(1Suppl.) (1Suppl.), 224 - 224, Japanese

  • ヒトCAKUTの原因遺伝子解析
    Morisada Naoya, 庄野 朱美, Nozu Kandai, 亀井 宏一, 伊藤 秀一, Iijima Kazumoto
    本邦症例における先天性腎尿路奇形(congenital anomalies of the kidney and urinary tract, CAKUT)の原因遺伝子解析を行った。症例は102家系で、腎外症状をともなわないnon-syndromic CAKUTは43家系(49例)、ともなうsyndromic CAKUTが59家系(74例)であった。遺伝子変異の同定率はnon-syndromic CAKUTで20.9%、syndromic CAKUTで30.5%であった。今回の検討ではPAX2やEYA1などの変異が原因遺伝子として同定されたが、原因不明例も多かった。この理由として、腎発生には多数の因子が関与していることが考えられる。ヒトCAKUTの全容は未だ明らかではなく、さらなる症例の集積が必要である。(著者抄録)
    発達腎研究会, Apr. 2014, 発達腎研究会誌, 22(1) (1), 27 - 29, Japanese
    [Refereed]
    Scientific journal

  • シクロスポリン投与下に再発をきたしたステロイド感受性ネフローゼ症候群の長期予後
    忍頂寺 毅史, 貝藤 裕史, 神吉 直宙, 松野下 夏樹, 大坪 裕美, 野津 寛大, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (公社)日本小児科学会, Feb. 2014, 日本小児科学会雑誌, 118(2) (2), 284 - 284, Japanese

  • 診断時に急性腎障害を合併した小児全身性エリテマトーデス患者の腎予後に関する検討
    石森 真吾, 貝藤 裕史, 神岡 一郎, 島 友子, 野津 寛大, 濱平 陽史, 中西 浩一, 田中 亮二郎, 吉川 徳茂, 飯島 一誠
    (公社)日本小児科学会, Feb. 2014, 日本小児科学会雑誌, 118(2) (2), 286 - 286, Japanese

  • Kazumoto Iijima, Mayumi Sako, Mari Saito Oba, Shuichi Ito, Hiroshi Hataya, Ryojiro Tanaka, Yoko Ohwada, Koichi Kamei, Kenji Ishikura, Nahoko Yata, Kandai Nozu, Masataka Honda, Hidefumi Nakamura, Michio Nagata, Yasuo Ohashi, Koichi Nakanishi, Norishige Yoshikawa
    Background and objectives An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine. Design, setting, participants, & measurements Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment. Results Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. Conclusion The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.
    AMER SOC NEPHROLOGY, Feb. 2014, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 9(2) (2), 271 - 278, English
    [Refereed]
    Scientific journal

  • Fu XJ, Morisada N, Hashimoto F, Taniguchi-Ikeda M, Hashimura Y, Ohtsubo H, Ninchoji T, Kaito H, Nozu K, Takahashi E, Nakanishi K, Kurahashi H, Iijima K
    2014, Human genome variation, 1, 14006
    [Refereed]

  • Hiroshi Kaito, Shingo Ishimori, Kandai Nozu, Yuko Shima, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima
    Background/Aims: Exercise-induced acute renal failure [exercise-induced acute kidney injury (EI-AKI)] is defined as AKI due to heavy anaerobic exercise. Although hypouricemia is known to be a risk factor for the onset of EI-AKI, a direct causal link between EI-AKI and serum uric acid has not been established. This study aimed to analyze urate transporter genes in patients with EI-AKI and its molecular mechanism. Methods: Genomic DNA and total RNA were isolated from peripheral blood leukocytes of patients with a history of EI-AKI. Mutations were analyzed by PCR and a direct sequencing method. We first analyzed the SLC22A12 gene, and then the SLC2A9 gene if no mutations were found in SLC22A12. Results: Seventeen patients were enrolled in this study and 16 had mutations: 15 in SLC22A12 and 1 in SLC2A9. Fourteen (82.4%) patients showed hypouricemia, and all of the patients with hypouricemia had either homozygous or compound heterozygous mutations in SLC22A12 or SLC2A9, which confirmed that all of them had renal hypouricemia. Two patients had heterozygous mutations of SLC22A12, and they were not accompanied by hypouricemia. One patient was found to have no mutations in SLC22A12 or SLC2A9. Conclusion: We were able to determine the genetic background of urate transporter genes in patients with EI-AKI. Decreased function of urate transporters, rather than decreased serum uric acid levels, may be of great importance for the onset of EI-AKI. © 2013 S. Karger AG, Basel.
    Oct. 2013, American Journal of Nephrology, 38(4) (4), 316 - 320, English
    [Refereed]
    Scientific journal

  • Taketsugu Hama, Koichi Nakanishi, Hironobu Mukaiyama, Yuko Shima, Hiroko Togawa, Mayumi Sako, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa
    A possible mechanism of cyclosporine (CsA) nephrotoxicity is tubular apoptosis. Endoplasmic reticulum (ER) stress has been shown to be an apoptosis activator. Glucose-regulated proteins 78 and 94 (GRP78, GRP94, respectively) are ER stress-induced chaperones. Eukaryotic translation initiation factor 2 alpha (EIF2 alpha) attenuates protein synthesis. If stress is prolonged, cells undergo apoptosis, inducing the production of GADD153, a transcription factor, which in turn downregulates anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Endoplasmic reticulum stress-related molecules were evaluated by real-time polymerase chain reaction (PCR) using renal biopsy tissues from 17 children with frequently relapsing nephrotic syndrome before and after 2 years of CsA therapy. GRP78, GRP94, eIF2 alpha, and Bcl-2 were significantly upregulated in renal biopsy tissues from children 2 years post-CsA treatment. However, there was almost no change in GADD153. Mean ratios of post- to pre-CsA expression of GRP78, GRP94, eIF2 alpha and Bcl-2 were 2.53, 1.80, 2.38 and 1.92, respectively. Post-CsA administration, GRP78 and eIF2 alpha were upregulated by up to sixfold, and GRP94 and Bcl-2 were upregulated by up to fourfold compared with the respective pre-CsA levels. There were significant correlations between GRP78, GRP94, eIF2 alpha, and Bcl-2 levels. These findings suggest that CsA induced an unfolded protein response due to ER stress, but did not cause apoptosis. An unfolded protein response due to ER stress induced by CsA may function in a defensive manner, with less apoptosis occurring under low-dose conditions. This finding is important for the rationale for CsA administration.
    SPRINGER, Jun. 2013, PEDIATRIC NEPHROLOGY, 28(6) (6), 903 - 909, English
    [Refereed]
    Scientific journal

  • Masafumi Hasui, Kazunari Kaneko, Shoji Tsuji, Yuka Isozaki, Takahisa Kimata, Yoshimi Nozu, Kandai Nozu, Kazumoto Iijima
    Multicystic dysplastic kidney (MCDK) is one of the most common congenital abnormalities of the kidney and urinary tract (CAKUT), although its pathophysiology remains unknown. Familial occurrence of MCDK suggests that mutations in genes associated with nephrogenesis are involved in the pathogenesis in at least some cases. Hepatocyte nuclear factor 1 beta (HNF1 beta) is a member of the homeodomain-containing super family of transcription factors, and is known to regulate tissue-specific gene expression in a number of organs including the kidneys, pancreas and liver. It has been recently postulated to be associated with CAKUT, including MCDK. We recently encountered a family with a deletion mutant of HNF1 beta, of which the 2nd son, the proband, developed bilateral MCDK resulting in renal loss of function in infancy while the 1st son developed unilateral MCDK. Their father has two normal kidneys. This family confirmed that mutations in the HNF1 beta gene are strongly associated with the development of MCDK. Furthermore, the fact that no clear phenotype-genotype correlation exists suggests that gene(s) other than HNF1 beta are also involved in nephrogenesis and the development of MCDK.
    DUSTRI-VERLAG DR KARL FEISTLE, Jun. 2013, CLINICAL NEPHROLOGY, 79(6) (6), 484 - 487, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Koichi Nakanishi, Taketsugu Hama, Hironobu Mukaiyama, Hiroko Togawa, Mayumi Sako, Hiroshi Kaito, Kandai Nozu, Ryojiro Tanaka, Kazumoto Iijima, Norishige Yoshikawa
    Some patients with IgA nephropathy (IgAN) achieve spontaneous remission even when not receiving medication. However, details on such remissions remain unknown. The aim of our study was to clarify this information in the clinical setting of childhood IgAN with minor glomerular abnormalities or focal mesangial proliferation (MGA/FMP). This study was a retrospective analysis of 96 children with MGA/FMP who did not receive medication from among the 555 patients with newly diagnosed childhood IgAN treated between January 1972 and December 2000. The Kaplan-Meier method and Cox proportional hazard model were used for the analysis. Of the 96 pediatric patients who did not receive medication, 57 (59.4 %) achieved spontaneous remission. The cumulative spontaneous remission rates among these patients were 57.5 and 77.4 % at 5 and 10 years, respectively, from onset. The mean time from onset to remission was 5.9 +/- 0.4 years. Clinical and histological findings were similar between the remission and non-remission groups. Of the 57 patients with spontaneous remissions, ten (17.5 %) also developed a recurrence of urinary abnormalities. The cumulative recurrence-free rates were 79.9 and 67.9 % at 5 and 10 years, respectively, after remission. The spontaneous remission rate in childhood IgAN with MGA/FMP was higher than expected. Our results suggest that physicians should consider the potential for spontaneous remission and refrain from very aggressive treatment in IgAN patients with MGA/FMP.
    SPRINGER, Jan. 2013, PEDIATRIC NEPHROLOGY, 28(1) (1), 71 - 76, English
    [Refereed]
    Scientific journal

  • SLC26A3 gene analysis in patients with Bartter and Gitelman syndromes and the clinical characteristics of patients with unidentified mutations
    Shingo Ishimori, Hiroshi Kaito, Natsuki Matsunoshita, Hiromi Otsubo, Fusako Hashimoto, Takeshi Ninchoji, Kandai Nozu, Naoya Morisada, Kazumoto Iijima
    We analyzed the SLC26A3 gene in patients with a clinical diagnosis of Bartter and Gitelman syndromes in whom genetic diagnoses could not be determined. We also examined the genetic and clinical characteristics of patients for whom genetic proof could not be obtained. The present study included 10 patients. With regard to genetic characteristics, 1 patient harbored a heterozygous mutation in the SLC12A3 gene (c.2573A> T, p.L858H), which was also reported in a previous report. With regard to clinical characteristics, 3 patients had abnormalities that were identified incidentally during medical examinations and other illnesses and 1 patient had polyhydramnios. One case of nephrocalcinosis was also noted. Eight patients were of below average height. Although we analyzed the SLC26A3 gene in these 10 patients, none were found to have pathological mutations. Investigation of the outcomes of these cases showed that examination findings had normalized and medication was no longer necessary for 3 patients, whereas hypokalemia and metabolic alkalosis were observed in another patient only in the presence of acute disease. We concluded that few patients develop illnesses because of SLC26A3 mutations. Other disease-related genes may also be involved. Although hypokalemia and metabolic alkalosis are clinical characteristics of Bartter and Gitelman syndromes, many other conditions also present such symptoms, and thus, differential diagnosis is of paramount importance.
    2013, Kobe Journal of Medical Sciences, 59(2) (2), E36 - E43, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Michelle Kwon, Tengis S. Pavlov, Kandai Nozu, Shauna A. Rasmussen, Daria V. Ilatovskaya, Alexandra Lerch-Gaggl, Lauren M. North, Hyunho Kim, Feng Qian, William E. Sweeney, Ellis D. Avner, Joe B. Blumer, Alexander Staruschenko, Frank Park
    Polycystic kidney diseases are the most common genetic diseases that affect the kidney. There remains a paucity of information regarding mechanisms by which G proteins are regulated in the context of polycystic kidney disease to promote abnormal epithelial cell expansion and cystogenesis. In this study, we describe a functional role for the accessory protein, G-protein signaling modulator 1 (GPSM1), also knownas activator of G-protein signaling 3, to act as a modulator of cyst progression in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD). A complete loss of Gpsm1in the Pkd1(V/V) mousemodel of ADPKD, which displays a hypomorphic phenotype of polycystin-1, demonstrated increased cyst progression and reduced renal function compared with age-matched cystic Gpsm1(+/+) and Gpsm1(+/-) mice. Electrophysiological studies identified a role by which GPSM1 increased heteromeric polycystin-1/polycystin-2 ion channel activity via G beta gamma subunits. In summary, the present study demonstrates an important role for GPSM1 in controlling the dynamics of cyst progression in an orthologous mouse model of ADPKD and presents a therapeutic target for drug development in the treatment of this costly disease.
    NATL ACAD SCIENCES, Dec. 2012, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(52) (52), 21462 - 21467, English
    [Refereed]
    Scientific journal

  • Hiroko Chikamoto, Motoshi Hattori, Nao Kuroda, Yuko Kajiho, Hideki Matsumura, Hiroshi Fujii, Kiyonobu Ishizuka, Masataka Hisano, Yuko Akioka, Kandai Nozu, Hiroshi Kaito, Maki Shimizu
    Chikamoto H, Hattori M, Kuroda N, Kajiho Y, Matsumura H, Fujii H, Ishizuka K, Hisano M, Akioka Y, Nozu K, Kaito H, Shimizu M. Pretransplantation combined therapy with plasmapheresis and rituximab in a second living-related kidney transplant pediatric recipient with a very high risk for focal segmental glomerulosclerosis recurrence. ?Pediatr Transplantation 2011. (c) 2011 John Wiley & Sons A/S. Abstract: Prophylactic PP can provide some protection against post-transplantation recurrences of FSGS, but it cannot prevent recurrences in all cases. Therefore, new preventive therapies are needed. We report on a 7.9-yr-old girl treated with pretransplantation prophylactic combined therapy consisting of four sessions of PP and one dose of rituximab before a second living-related KTX. The patient had a very high risk of post-transplantation FSGS recurrence because this had occurred after the first KTX. During the 36 months since the second transplantation, she has had no evidence of proteinuria or significant infectious complications. Although our experience is too preliminary to draw any generalizable conclusions, pretransplantation combined therapy with PP and rituximab might be a possible option for the prevention of FSGS recurrence in very high-risk recipients undergoing living-donor KTXs.
    WILEY-BLACKWELL, Nov. 2012, PEDIATRIC TRANSPLANTATION, 16(7) (7), E286 - E290, English
    [Refereed]
    Scientific journal

  • Kazumoto Iijima, Tomonosuke Someya, Shuichi Ito, Kandai Nozu, Koichi Nakanishi, Kentaro Matsuoka, Hirofumi Ohashi, Michio Nagata, Koichi Kamei, Satoshi Sasaki
    The renal prognosis of patients with Wilms' tumor, aniridia, genito-urinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS. Pediatrics 2012; 129: e1621-e1625
    AMER ACAD PEDIATRICS, Jun. 2012, PEDIATRICS, 129(6) (6), E1621 - E1625, English
    [Refereed]
    Scientific journal

  • Hashimura Y, Kaito H, Nozu K, Shima Y, Nakanishi K, Iijima K, Yoshikawa N
    Atypical membranoproliferative glomerulonephritis (MPGN) is considered to progress to typical MPGN, and it is believed that it can be treated with corticosteroids. However, consensus that atypical MPGN is a continuum of morphologic manifestations of typical MPGN cannot be reached. Herein, we report two cases of atypical MPGN with opposite clinical course. Case 1 was a 4-year-old boy with macrohematuria and proteinuria with no prodromal symptoms. His serum C3 level had abruptly dropped, and renal biopsy confirmed a diagnosis of atypical MPGN. After performing kidney biopsy, his urinary abnormality improved and his C3 level had normalized 1 year after onset without medication. At the most recent follow-up, neither proteinuria nor hematuria was detected. Case 2 was a 7-year-old girl with microhematuria and proteinuria at her school urinary screening. Her first biopsy finding was similar to dense deposit disease, and the second biopsy showed atypical MPGN. Oral corticosteroids were started from this point, but heavy proteinuria and hypocomplementemia could not be improved sufficiently. We immediately performed third kidney biopsy and diagnosed typical MPGN. These findings suggest that the indication of therapy for atypical MPGN should be re-examined. Aggressive therapy such as steroid administration is not necessarily essential and effective for therapeutic intervention of all atypical MPGN. Moreover, atypical MPGN may involve different etiologic and pathogenetic factors, rather than a continuum of morphologic manifestations of MPGN.
    May 2012, CEN case reports, 1(1) (1), 34 - 38, English, Domestic magazine
    [Refereed]
    Scientific journal

  • 石森 真吾, 大坪 裕美, 橋本 総子, 忍頂寺 毅史, 橋村 裕也, 貝藤 裕史, 森貞 直哉, 野津 寛大, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2012, 日本小児腎臓病学会雑誌, 25(1Suppl.) (1Suppl.), 191 - 191, Japanese

  • 橋村 裕也, 野津 寛大, 貝藤 裕史, 橋本 総子, 大坪 裕美, 石森 真吾, 忍頂寺 毅史, 森貞 直哉, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2012, 日本小児腎臓病学会雑誌, 25(1Suppl.) (1Suppl.), 193 - 193, Japanese

  • Naoto Nishizaki, Shuichiro Fujinaga, Daishi Hirano, Hiroaki Kanai, Hitoshi Kaya, Yoshiyuki Ohtomo, Toshiaki Shimizu, Kandai Nozu, Kazunari Kaneko
    Although renal hypouricemia is mostly asymptomatic, it is known to present a high risk of exercise-induced acute renal failure, especially in young males. However, there is little information regarding the clinical features of urolithiasis as a complication in childhood renal hypouricemia. Here we report a 4-year-old female with idiopathic renal hypouricemia who presented with macroscopic hematuria due to obstructive calcium oxalate urolithiasis. She was treated successfully with percutaneous nephrolithotripsy and thereafter hematuria disappeared. Sequence analysis of the patient and her family's URAT1 gene confirmed a nonsense mutation in exon 4 (W258X). To the best of our knowledge, this is the youngest case of hereditary renal hypouricemia caused by URAT1 gene mutation, which was found by hematuria due to calcium oxalate urolithiasis.
    DUSTRI-VERLAG DR KARL FEISTLE, Feb. 2012, CLINICAL NEPHROLOGY, 77(2) (2), 161 - 163, English
    [Refereed]
    Scientific journal

  • Keisuke Otsubo, Hirokazu Kanegane, Yoshiro Kamachi, Ichiro Kobayashi, Ikuya Tsuge, Masue Imaizumi, Yoji Sasahara, Akira Hayakawa, Kandai Nozu, Kazumoto Iijima, Shuichi Ito, Reiko Horikawa, Yoshinori Nagai, Kiyoshi Takatsu, Hisashi Mori, Hans D. Ochs, Toshio Miyawaki
    Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disorder caused by mutations in the FOXP3 gene, which plays a key role in the generation of CD4(+)CD25(+)regulatory T (Treg) cells. We selected CD127 as the surface marker of Treg cells to illustrate the development and function of Treg cells in IPEX syndrome. CD4(+)CD25(+)FOXP3(+) T cells, the putative Treg cells, were almost completely absent in all patients. Importantly, a substantial number of CD4(+)CD25(+)CD127(low) T cells were observed in 3 IPEX patients with hypomorphic mutations in the FOXP3 gene. We demonstrated that CD4(+)CD25(+)CD127(low) T cells isolated from these 3 patients exhibited an appreciable suppressive activity on effector T cell proliferation, although less than that displayed by Treg cells from healthy controls. These results suggest that genetically altered FOXP3 can drive the generation of functionally immature Treg cells, but that intact FOXP3 is necessary for the complete function of Treg cells. (C) 2011 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Oct. 2011, CLINICAL IMMUNOLOGY, 141(1) (1), 111 - 120, English
    [Refereed]
    Scientific journal

  • 運動後急性腎不全とPRESの合併を反復し、GLUT9遺伝子複合ヘテロ接合体変異を同定しえた腎性低尿酸血症の1例
    島 友子, 野津 寛大, 戸川 寛子, 貝藤 裕史, 飯島 一誠, 中西 浩一, 吉川 徳茂
    日本小児腎不全学会, Jul. 2011, 日本小児腎不全学会雑誌, 31, 102 - 102, Japanese

  • Kevin R. Regner, Kandai Nozu, Stephen M. Lanier, Joe B. Blumer, Ellis D. Avner, William E. Sweeney, Frank Park
    The intracellular mechanisms underlying renal tubular epithelial cell proliferation and tubular repair following ischemia-reperfusion injury (IRI) remain poorly understood. In this report, we demonstrate that activator of G-protein signaling 3 (AGS3), an unconventional receptor-independent regulator of heterotrimeric G-protein function, influences renal tubular regeneration following IRI. In rat kidneys exposed to IRI, there was a temporal induction in renal AGS3 protein expression that peaked 72 h after reperfusion and corresponded to the repair and recovery phase following ischemic injury. Renal AGS3 expression was localized predominantly to the recovering outer medullary proximal tubular cells and was highly coexpressed with Ki-67, a marker of cell proliferation. Kidneys from mice deficient in the expression of AGS3 exhibited impaired renal tubular recovery 7 d following IRI compared to wild-type AGS3-expressing mice. Mechanistically, genetic knockdown of endogenous AGS3 mRNA and protein in renal tubular epithelial cells reduced cell proliferation in vitro. Similar reductions in renal tubular epithelial cell proliferation were observed following incubation with gallein, a selective inhibitor of G beta gamma subunit activity, and lentiviral overexpression of the carboxyl-terminus of G-protein-coupled receptor kinase 2 (GRK2ct), a scavenger of G beta gamma subunits. In summary, these data suggest that AGS3 acts through a novel receptor-independent mechanism to facilitate renal tubular epithelial cell proliferation and renal tubular regeneration.-Regner, K. R., Nozu, K., Lanier, S. M., Blumer, J. B., Avner, E. D., Sweeney, Jr., W. E., Park, F. Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents. FASEB J. 25, 1844-1855 (2011). www.fasebj.org
    FEDERATION AMER SOC EXP BIOL, Jun. 2011, FASEB JOURNAL, 25(6) (6), 1844 - 1855, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Kandai Nozu, Yoshimi Nozu, Hiroko Togawa, Hiroshi Kaito, Masafumi Matsuo, Kazumoto Iijima, Koichi Nakanishi, Norishige Yoshikawa
    Renal hypouricemia (RHU) is a hereditary disease that predisposes affected people to exercise-induced acute renal failure (EIARF). In most patients with RHU, the disorder is caused by loss-of-function mutations in SLC22A12 (solute carrier family 22, member 12), which encodes urate transporter 1 (URAT1). Patients with RHU without any mutations in the URAT1 gene were recently found to have a mutation in the glucose transporter 9 (GLUT9) gene (SLC2A9 [solute carrier family 2, member 9]). Central nervous system complications seem to be rare in patients with RHU with SLC22A12 mutations. Here, we report the case of a girl with severe RHU (serum urate: 5.9 mu mol/L [0.1 mg/dL]) associated with recurrent EIARF in whom the disease was caused by a compound heterozygous mutation in SLC2A9, a nonsense mutation in the paternal allele (p.G207X in exon 7), and a large duplication (c.1-2981_1204 + 16502) in the maternal allele detected by reverse-transcription polymerase chain reaction (PCR), semiquantitative PCR, long PCR, and direct sequencing. The episodes of EIARF were complicated by posterior reversible encephalopathy syndrome (PRES), which suggested a relationship between PRES and GLUT9 or severe hypouricemia. This is the second report of mutations of both alleles of SLC2A9 that resulted in severe hypouricemia. Our findings indicate that even a nonsense mutation responsible for the heterozygous status of SLC2A9 did not cause severe hypouricemia, and they lend support to previous speculation that mutations of both SLC2A9 alleles cause severe hypouricemia. Our case shows that GLUT9, unlike URAT1, may play a specific role in exercise-induced PRES. Pediatrics 2011; 127:e1621-e1625
    AMER ACAD PEDIATRICS, Jun. 2011, PEDIATRICS, 127(6) (6), E1621 - E1625, English
    [Refereed]
    Scientific journal

  • Kazumichi Fujioka, Ichiro Morioka, Kandai Nozu, Masashi Nishimoto, Mariko Amano, Mizuki Tagami, Shigeru Honda, Naoki Yokoyama, Hideto Yamada, Kazumoto Iijima, Masafumi Matsuo
    WILEY-BLACKWELL, Jun. 2011, PEDIATRICS INTERNATIONAL, 53(3) (3), 406 - 408, English
    [Refereed]
    Scientific journal

  • 血清アルブミン値と組織所見に基づいた小児紫斑病性腎炎の治療戦略
    忍頂寺 毅史, 貝藤 裕史, 橋村 裕也, 神岡 一郎, 野津 寛大, 中西 浩一, 田中 亮二郎, 吉川 徳茂, 飯島 一誠
    (一社)日本腎臓学会, May 2011, 日本腎臓学会誌, 53(3) (3), 364 - 364, Japanese

  • 島 友子, 中西 浩一, 戸川 寛子, 吉川 徳茂, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2011, 日本小児腎臓病学会雑誌, 24(1) (1), 125 - 126, Japanese

  • 貝藤 裕史, 野津 寛大, 忍頂寺 毅史, 橋村 裕也, 飯島 一誠, 松尾 雅文, 川西 智子, 城 謙輔, 吉川 徳茂
    (一社)日本小児腎臓病学会, Apr. 2011, 日本小児腎臓病学会雑誌, 24(1) (1), 133 - 133, Japanese

  • Iijima Kazumoto, Sako Mayumi, Kimura Toshimi, Hattori Motoshi, Kamei Koichi, Nozu Kandai, Shishido Seiichiro, Aikawa Atsushi, Morita Ken, Gotoh Yoshimitsu, Wada Naohiro, Ohtsuka Yasufumi, Nagata Michio, Saito Mari, Honda Masataka, Tsuchida Nao, Nakamura Hidehumi
    We conducted an open-label, single-arm multicenter study to evaluate the efficacy, safety and pharmacokinetics of MMF in Japanese pediatric renal allograft recipients, comparing with historical data in United Sates pediatric and Japanese adult renal allograft recipients. The primary efficacy outcome was the proportion of patients experiencing a biopsy-proven acute rejection episode within the first 6 months post-transplantation. Secondary efficacy outcomes were the proportion of patients who lost their graft by 12 months, the proportion of patients who died at 12 months.
     25 patients (2 to < 18 years) received MMF 300-600 mg/m2 b.i.d. concomitantly with calcineurin inhibitor and corticosteroids with or without antilymphocyte antibody induction. Six patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) acute rejection episode within the first 6 months post-transplantation. One year after transplantation, patient and graft survival were 100% and 100%, respectively. Seventeen patients (68%) experienced adverse events. The most common adverse events related to MMF involved the infection associated with cytomegalovirus virus. Withdrawal of MMF due to adverse event was necessary in two patients. All adverse events associated with MMF were acceptable. The dosing regimen of MMF 300-600 mg/m2 b.i.d. achieved the targeted in the first 3 months post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 48.7 ± 27.6 μg hr/ml. This was similar with AUC0-12 of Japanese adult renal transplant recipients treated with MMF 2,000 mg b.i.d. The time course of estimated AUC0-12 showed no clinically difference with that of United Sates pediatric renal allograft recipients treated with MMF 600mg/m2 b.i.d.
     Administration of MMF 300-600mg/m2 b.i.d. may be effective in prevention of acute rejection and be tolerant in Japanese pediatric renal transplant recipients, although this study has the limitation of study design and small patients' numbers. This dosing regimen provided predictable pharmacokinetics, too.
    The Japanese Society for Pediatric Nephrology, Apr. 2011, Nihon Shoni Jinzobyo Gakkai Zasshi, 24(1) (1), 36-46 - 46, Japanese
    Scientific journal

  • Takeshi Ninchoji, Hiroshi Kaito, Kandai Nozu, Yuya Hashimura, Kyoko Kanda, Ichiro Kamioka, Yuko Shima, Kiyoshi Hamahira, Koichi Nakanishi, Ryojiro Tanaka, Norishige Yoshikawa, Kazumoto Iijima, Masafumi Matsuo
    The management of Henoch-Schonlein purpura nephritis (HSPN) is controversial. It has been revealed that some patients develop end-stage renal disease and aggressive treatment with drugs such as steroids is increasing, and some of them may be overzealous. At our institutes, our treatment decisions are based on the clinical and pathological severity of the case in an attempt to limit the indications for aggressive therapies such as steroids and immunosuppressive agents. Here, we retrospectively examined the efficacy of treatment for HSPN. Renal biopsy was performed in patients with nephrotic syndrome or persistent proteinuria for more than 3 months and patients were classified by treatment. Patients (n = 31) with moderately severe HSPN (histological grade I-III and serum albumin [Alb] > 2.5 g/dl) were treated with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. Patients (n = 19) with HSPN exceeding grade III or Alb a parts per thousand currency signaEuro parts per thousand 2.5 g/dl received combination therapy comprising prednisolone, immunosuppressants, warfarin, and dipyridamole. All patients showed resolution of proteinuria without renal dysfunction during the observation period (3.76 +/- 0.37 years). Our findings support those of some earlier reports that treatment strategies for HSPN should depend on the histological and clinical severity. Furthermore, aggressive therapies, particularly combination therapies, are unnecessary for moderate-severe HSPN.
    SPRINGER, Apr. 2011, PEDIATRIC NEPHROLOGY, 26(4) (4), 563 - 569, English
    [Refereed]
    Scientific journal

  • Yi-Fen Lo, Kandai Nozu, Kazumoto Iijima, Takahiro Morishita, Che-Chung Huang, Sung-Sen Yang, Huey-Kang Sytwu, Yu-Wei Fang, Min-Hua Tseng, Shih-Hua Lin
    Background and objectives Gitelman's syndrome (GS) is an autosomal recessive renal tubular disorder caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive Na+-Cl- cotransporter (NCC). Despite meticulous sequencing of genomic DNA, approximately one-third of GS patients are negative or heterozygotes for the known mutations. Design, Setting, Participants, & Measurements Because blood leukocytes express NCC mRNA, we evaluate whether deep intronic mutations contribute to GS patients with uniallelic or undetectable SLC12A3 mutations. Twenty-nine patients with GS (men/women = 16/13), including eight negative and 21 uniallelic SLC12A3 mutations from 19 unrelated families, and normal controls were enrolled in an academic medical center. Analysis of cDNA from blood leukocytes, sequencing of the corresponding introns of genomic DNA for abnormal transcript, and analysis of NCC protein expression from renal biopsy were performed. Results We identified nine Taiwan aboriginal patients carrying c.1670-191C -> T mutations in intron 13 and 10 nonaboriginal patients carrying c.2548+253C -> T mutations in intron 21 from 14 families (14/19). These two mutations undetected in 100 healthy subjects created pseudoexons containing new premature termination codons. Haplotype analysis with markers flanking SLC12A3 revealed that both mutations did not have founder effects. Apical NCC expression in the DCT of renal tissue was markedly diminished in two patients carrying deep intronic mutations. Conclusions Deep intronic mutations in SLC12A3 causing defective NCC expression can be identified with the RNA-based approach in patients with GS. c.1670-191C -> T and c.2548+253C -> T are hot spot mutations that can be screened in GS patients with uniallelic or negative SLC12A3 mutations. Clin J Am Soc Nephrol 6: 630-639, 2011. doi: 10.2215/CJN.06730810
    AMER SOC NEPHROLOGY, Mar. 2011, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 6(3) (3), 630 - 639, English
    [Refereed]
    Scientific journal

  • Hiroko Togawa, Koichi Nakanishi, Hironobu Mukaiyama, Taketsugu Hama, Yuko Shima, Mayumi Sako, Masayasu Miyajima, Kandai Nozu, Kazuhiro Nishii, Shizuko Nagao, Hisahide Takahashi, Kazumoto Iijima, Norishige Yoshikawa
    Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Sako M, Miyajima M, Nozu K, Nishii K, Nagao S, Takahashi H, Iijima K, Yoshikawa N. Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. Am J Physiol Renal Physiol 300: F511-F520, 2011. First published November 17, 2010; doi:10.1152/ajprenal.00038.2010.-In polycystic kidney disease (PKD), cyst lining cells show polarity abnormalities. Recent studies have demonstrated loss of cell contact in cyst cells, suggesting induction of epithelial-to-mesenchymal transition (EMT). Recently, EMT has been implicated in the pathogenesis of PKD. To explore further evidence of EMT in PKD, we examined age-and segment-specific expression of adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at 0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained with segment-specific markers and antibodies against E-cadherin, Snail1, beta-catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real-time PCR. Vimentin, fibronectin, and alpha-smooth muscle actin (alpha-SMA) expressions were assessed as mesenchymal markers. E-cadherin expression pattern was correlated with the disease pathology in that tubule segments showing the highest expression in control had much severer cyst formation in PCK rats. In PCK rats, E-cadherin and beta-catenin in cystic tubules was attenuated and localized to lateral areas of cell-cell contact, whereas nuclear expression of Snail1 increased in parallel with cyst enlargement. Some epithelial cells in large cysts derived from these segments, especially in adjacent fibrotic areas, showed positive immunoreactivity for vimentin and fibronectin. In conclusion, these findings suggest that epithelial cells in cysts acquire mesenchymal features in response to cyst enlargement and participate in progressive renal fibrosis. Our study clarified the nephron segment-specific cyst profile related to EMT in PCK rats. EMT may play a key role in polycystic kidney disease.
    AMER PHYSIOLOGICAL SOC, Feb. 2011, AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 300(2) (2), F511 - F520, English
    [Refereed]
    Scientific journal

  • 巣状メサンギウム増殖を示す小児IgA腎症に対するACEIの治療反応性
    島 友子, 中西 浩一, 濱 武継, 向山 弘展, 戸川 寛子, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (公社)日本小児科学会, Feb. 2011, 日本小児科学会雑誌, 115(2) (2), 268 - 268, Japanese

  • Hiroko Togawa, Koichi Nakanishi, Hironobu Mukaiyama, Taketsugu Hama, Yuko Shima, Mayumi Sako, Masayasu Miyajima, Kandai Nozu, Kazuhiro Nishii, Shizuko Nagao, Hisahide Takahashi, Kazumoto Iijima, Norishige Yoshikawa
    In polycystic kidney disease (PKD), cyst lining cells show polarity abnormalities. Recent studies have demonstrated loss of cell contact in cyst cells, suggesting induction of epithelial-to-mesenchymal transition (EMT). Recently, EMT has been implicated in the pathogenesis of PKD. To explore further evidence of EMT in PKD, we examined age- and segment-specific expression of adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at 0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained with segment-specific markers and antibodies against E-cadherin, Snail1, β-catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real-time PCR. Vimentin, fibronectin, and α-smooth muscle actin (α-SMA) expressions were assessed as mesenchymal markers. E-cadherin expression pattern was correlated with the disease pathology in that tubule segments showing the highest expression in control had much severer cyst formation in PCK rats. In PCK rats, E-cadherin and β-catenin in cystic tubules was attenuated and localized to lateral areas of cell-cell contact, whereas nuclear expression of Snail1 increased in parallel with cyst enlargement. Some epithelial cells in large cysts derived from these segments, especially in adjacent fibrotic areas, showed positive immunoreactivity for vimentin and fibronectin. In conclusion, these findings suggest that epithelial cells in cysts acquire mesenchymal features in response to cyst enlargement and participate in progressive renal fibrosis. Our study clarified the nephron segment-specific cyst profile related to EMT in PCK rats. EMT may play a key role in polycystic kidney disease. Copyright © 2011 the American Physiological Society.
    Feb. 2011, American Journal of Physiology - Renal Physiology, 300(2) (2), F511 - F520, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Koichi Nakanishi, Koichi Kamei, Hiroko Togawa, Kandai Nozu, Ryojiro Tanaka, Satoshi Sasaki, Kazumoto Iijima, Norishige Yoshikawa
    Background. The prognosis of children with severe IgA nephropathy showing diffuse mesangial proliferation is poor. However, the prognosis can be improved by combination therapy (prednisolone + azathioprine or mizoribine + warfarin + dipyridamole) or prednisolone alone over a 2-year period, and disappearance of glomerular IgA deposits is often observed. Details of the incidence and clinicopathological significance of glomerular IgA disappearance remain unclear. Methods. To investigate this phenomenon, we retrospectively screened and analysed 124 consecutive children (age <= 18 years at first biopsy) with newly diagnosed severe IgA nephropathy showing diffuse mesangial proliferation, who received combination therapy or prednisolone alone for 2 years and underwent repeat biopsies. Results. Among these patients, 90 received combination therapy, and 34 received prednisolone alone. After 2 years of treatment, 27 of the patients (21.8%) showed disappearance of glomerular IgA. Logistic analysis showed that IgA disappearance was associated with less severe urinary protein excretion at the end of treatment. Kaplan-Meier analysis of the long-term course revealed a significant difference in proteinuria-free survival after the 2-year treatment period between the patients with IgA disappearance and those without (P = 0.008; log-rank test). The Cox proportional hazards model showed that disappearance of glomerular IgA after the treatment was a factor significantly associated with proteinuria-free survival in both univariate and multivariate analyses. Conclusions. The present results suggest that disappearance of IgA after 2 years of treatment indicates milder disease severity, even in patients with diffuse mesangial proliferation, and is a prognostic factor related to proteinuria-free survival.
    OXFORD UNIV PRESS, Jan. 2011, NEPHROLOGY DIALYSIS TRANSPLANTATION, 26(1) (1), 163 - 169, English
    [Refereed]
    Scientific journal

  • Kyoko Kanda, Kandai Nozu, Hiroshi Kaito, Kazumoto Iijima, Koichi Nakanishi, Norishige Yoshikawa, Takeshi Ninchoji, Yuya Hashimura, Masafumi Matsuo, Michael L. Moritz
    Post-operative hyponatremia is a common complication in children which results from hypotonic fluid administration in the presence of arginine vasopressin (AVP) excess. We evaluated the relationship between the change in serum sodium and AVP levels following percutaneous renal biopsy in children receiving either hypotonic or isotonic fluids. This study was prompted after we encountered a patient who developed near-fatal hyponatremic encephalopathy following a renal biopsy while receiving hypotonic fluids. The relationship between the change in serum sodium and AVP levels was evaluated prior to (T0) and at 5 h (T5) following a percutaneous renal biopsy in 60 children receiving either hypotonic (0.6% NaCl, 90 mEq/L) or isotonic fluids (0.9% NaCl, 154 mEq/L). The proportion of patients with elevated AVP levels post-procedure was similar between those receiving 0.6 or 0.9% NaCl (30 vs. 26%). Patients receiving 0.6% NaCl with elevated AVP levels experienced a fall in serum sodium of 1.9 +/- 1.5 mEq/L, whereas those receiving 0.9% NaCl had a rise in serum sodium of 0.85 +/- 0.34 mEq/L with no patients developing hyponatremia. There were no significant changes in serum sodium levels in patients with normal AVP concentrations post-procedure in either group. In conclusion, elevated AVP levels were common among our patients following a percutaneous renal biopsy. Isotonic fluids prevented a fall in serum sodium and hyponatremia, while hypotonic fluids did not.
    SPRINGER, Jan. 2011, PEDIATRIC NEPHROLOGY, 26(1) (1), 99 - 104, English
    [Refereed]
    Scientific journal

  • [Bartter's syndrome].
    Nozu K
    2011, Nihon Jinzo Gakkai shi, 53(2) (2), 163 - 168
    [Refereed]

  • Yorihiro Iwasaki, Makio Takahashi, Kandai Nozu, Sadayuki Matsumoto, Hiroyuki Koshiyama
    A 49-year-old otherwise healthy man was admitted to our hospital because of repeated generalized convulsions after influenza A virus infection. His family history was notable for consanguinity of parents. Initial laboratory tests revealed metabolic alkalosis with hypomagnesemia, as well as an elevated high density lipoprotein cholesterol level. He was diagnosed with Gitelman's syndrome and cholesteryl ester transfer protein deficiency by identifying homozygous mutations of causative genes, SLC12A3 and CETP, respectively. These two genes are located in the vicinity on chromosome 16, suggesting the possibility of autozygosity. This is the first case report highlighting the co-existence of these genetic disorders.
    JAPAN SOC INTERNAL MEDICINE, 2011, INTERNAL MEDICINE, 50(19) (19), 2179 - 2183, English
    [Refereed]
    Scientific journal

  • Kimata Takahisa, Hasui Masahumi, Yamasita Miyoko, Kaneko Kazunari, Nozu Kandai, Iijima Kazumoto
    Dent disease is characterized by progressive proximal renal tubulopathy with hypercalciuria, low-molecular-weight proteinuria, and nephrocalcinosis. While nearly 60% of cases are reported to be caused by mutations in CLCN5 gene located on Xp11.22 and 10∼15% of cases are caused by mutations in OCRL1 gene located on Xq26.1, causes of the remaining 25∼30% of cases are still unknown.
     We here report the case of sibling with Dent disease having no mutations of OCRL1 and CLCN5 and suggest an autosomal fashion of inheritance of this disease.
     Case report: A 13 year-old brother and his 10-year-old sister were referred to us for further evaluation of asymptomatic tubular proteinuria detected at school screening program in Japan. Their past medical histories and family history were unremarkable. They were the first and the third products of the five siblings by healthy unrelated Japanese parents. Their physical examinations at referral revealed no abnormal findings whereas their urinary findings demonstrated increased concentrations of β2-microglobulin (β2MG) without significant hematuria or hypercalciuria. Blood tests showed normal values including serum creatinine, electrolytes, and proteins and ultrasound examinations did not detect any abnormal findings on their urinary tracts. Urinary levels of β2MG in their mother and other siblings were also within normal values.
     Based on these findings, the diagnoses of Dent disease were made on them. They have been followed-up periodically for 3 years by now to check their values of urinary β2MG which revealed consistent abnormal values: the brother demonstrated the values between 560μg/L and 1,830μg/L (normal: 30∼340μg/L) while the sister's values varied from 317μg/L to 23,550μg/L. Their sequence analyses of CLCN5 and OCRL1 did not show any mutations. Thus, we suggest that some patients with Dent disease show autosomal inheritance.
    The Japanese Society for Pediatric Nephrology, 2011, Nihon Shoni Jinzobyo Gakkai Zasshi, 24(1) (1), 92 - 95, Japanese

  • Molecular analysis of TSC2/PKD1 contiguous gene deletion syndrome
    Yoshinobu Oyazato, Kazumoto Iijima, Mitsuru Emi, Takashi Sekine, Koichi Kamei, Junichi Takanashi, Hideto Nakao, Yoshiyuki Namai, Kandai Nozu, Masafumi Matsuo
    Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. TSC2 lies immediately adjacent to PKD1 and large heterozygous deletions can result in the TSC2/PKD1 contiguous gene syndrome (PKDTS). PKDTS has been identified in patients with TSC and early-onset severe ADPKD. However, genetic diagnosis with conventional methods proved to be difficult because its genetic aberrations are large monoallelic mutations. Methods: In the study presented here, we used both multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array-CGH) for four PKDTS patients. Results: We were able to detect large heterozygous deletions including TSC2 and PKD1 by both of MLPA and array-CGH in all four patients. And in two patients, array-CGH identified relatively large genomic aberrations (RAB26, NTHL1, etc.), that extended outside of TSC2 or PKD1. Conclusion: The identical results obtained with these two completely different methods show that both constitute highly reliable strategies. Only a few studies have determined the breakpoints of large deletions in this disease and ours is the first to have identified the breakpoints by using array-CGH. We suggest that these methods are not only useful for the diagnosis of PKDTS but also for elucidation of its molecular mechanism.
    2011, Kobe Journal of Medical Sciences, 57(1) (1), E1 - E10, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kandai Nozu, Kazumoto Iijima, Kyoko Kanda, Koichi Nakanishi, Norishige Yoshikawa, Kenichi Satomura, Hiroshi Kaito, Yuya Hashimura, Takeshi Ninchoji, Hiroshi Komatsu, Koichi Kamei, Ritsuko Miyashita, Masaaki Kugo, Hiroshi Ohashi, Hajime Yamazaki, Hiroyo Mabe, Asa Otsubo, Takashi Igarashi, Masafumi Matsuo
    Context: Our understanding of inherited salt-losing tubulopathies has improved with recent advances in molecular genetics. However, the terminology of Bartter syndrome and Gitelman syndrome does not always accurately reflect their pathophysiological basis or clinical presentation, and some patients are difficult to diagnose from their clinical presentations. Objective: In the present study, we conducted molecular analysis and diuretic tests for patients with inherited salt-losing tubulopathies to clarify the pharmacological characteristics of these disorders. Patients: We detected mutations and subsequently conducted diuretic tests using furosemide and thiazide for 16 patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine with CLCNKB; and three with SLC12A3). Results: Patients with SLC12A1 mutations showed no response to furosemide, whereas those with SLC12A3 mutations showed no response to thiazide. However, patients with CLCNKB mutations showed no response to thiazide and a normal response to furosemide, and those with KCNJ1 mutations showed a good response to both diuretics. This study revealed the following characteristics of these disorders: 1) subjects with CLCNKB mutations showed one or more biochemical features of Gitelman syndrome (including hypomagnesemia, hypocalciuria, and fractional chloride excretion insensitivity to thiazide administration); and 2) subjects with KCNJ1 mutations appeared to show normal fractional chloride excretion sensitivity to furosemide and thiazide administration. Conclusions: These results indicate that these disorders are difficult to distinguish in some patients, even when using diuretic challenge. This clinical report provides important findings that can improve our understanding of inherited salt-losing tubulopathies and renal tubular physiology. (J Clin Endocrinol Metab 95: E511-E518, 2010)
    ENDOCRINE SOC, Dec. 2010, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 95(12) (12), E511 - E518, English
    [Refereed]
    Scientific journal

  • 島 友子, 野津 寛大, 戸川 寛子, 貝藤 裕史, 飯島 一誠, 松尾 雅文, 中西 浩一, 吉川 徳茂
    (一社)日本小児腎臓病学会, Nov. 2010, 日本小児腎臓病学会雑誌, 23(2) (2), 229 - 229, Japanese

  • Kajiho Yuko, Ueda Hiroaki, Mizutani Makoto, Taniguchi Kimiko, Furuyama Masayuki, Ishizuka Kiyonobu, Fujii Hiroshi, Chikamoto Hiroko, Akioka Yuko, Oka Masashi, Nozu Kandai, Iijima Kazumoto, Hattori Motoshi
    Thin basement membrane nephropathy (TBMN) is characterized by both microscopic hematuria clinically and diffusely thinned glomerular basement membrane pathologically. TBMN has been known to have a good renal prognosis which rarely induces end stage renal disease (ESRD) so far. However, it was reported that heterozygous mutations in COL4A3 and COL4A4, responsible for autosomal recessive Alport syndrome (ARAS), were found in about 40% of TBMN and some of them could progress to ESRD. We report here that two patients with ARAS received living renal transplantation from TBMN donors and heterozygous mutations in COL4A3 or COL4A4 were found in the donors after the transplantation. We confirmed that the kidney function of the donors was good before transplantation, and has been kept good till now. Heredity renal disease patients may have no choice but to receive kidneys from mutation career donors, if they hope living donor renal transplantation. In those cases, we should examine donors carefully, including urinalysis, kidney functions and genome analysis before transplantation, and need careful follow-up after transplantation.
    The Japanese Society for Pediatric Nephrology, Nov. 2010, Nihon Shoni Jinzobyo Gakkai Zasshi, 23(2) (2), 29-33 - 118, Japanese
    [Refereed]
    Scientific journal

  • Kazumoto Iijima, Kandai Nozu, Koichi Kamei, Makiko Nakayama, Shuichi Ito, Kentaro Matsuoka, Tsutomu Ogata, Hiroshi Kaito, Koichi Nakanishi, Masafumi Matsuo
    The course of renal involvement and hearing loss is much milder in most female X-linked Alport syndromes than in male patients. We examined the molecular mechanism of development of the disease in a female patient with severe Alport syndrome. The patient showed heavy proteinuria, hematuria, neurosensory hearing loss and primary amenorrhea. Renal biopsy findings of electron microscopy and immunostaining of the alpha 5 chain of type IV collagen indicated a female X-linked Alport syndrome. G-banding chromosomal analysis showed a t(X;1)(q22.3;p36.32) balanced translocation. Analysis of the collagen type IV (COL4A5) gene by genomic DNA sequencing, complementary DNA (cDNA) sequencing and multiplex ligation-dependent probe amplification assay showed no mutations or deletions/duplications of the gene. However, fluorescence in situ hybridization using the probes for exon 1 and exon 51 of the COL4A5 gene showed disruption of one copy of the gene. Replication R-banding chromosomal analysis indicated preferential inactivation of the normal X chromosome. This is the first report of severe Alport syndrome in a female patient carrying a balanced translocation between the chromosome X and 1 producing the disruption of one copy of COL4A5 gene and silencing of the other copy because of preferential inactivation of the normal X chromosome. Chromosomal abnormalities should be considered in female patients with severe forms of Alport syndrome.
    SPRINGER, Oct. 2010, PEDIATRIC NEPHROLOGY, 25(10) (10), 2165 - 2170, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 幼少時発症のFibronectin腎症でFN1遺伝子に変異のあった1例
    川西 智子, 笠原 正登, 森 潔, 横井 秀基, 桑原 孝成, 城 謙輔, 上杉 憲子, 長田 道夫, 野津 寛大, 飯島 一誠, 向山 政志, 中尾 一和
    (一社)日本腎臓学会, Aug. 2010, 日本腎臓学会誌, 52(6) (6), 811 - 811, Japanese

  • Naoya Morisada, Nanna Dahl Rendtorff, Kandai Nozu, Takahiro Morishita, Takayuki Miyakawa, Tohru Matsumoto, Satoshi Hisano, Kazumoto Iijima, Lisbeth Tranebjaerg, Akira Shirahata, Masafumi Matsuo, Koichi Kusuhara
    A 7-year-old Japanese girl with conductive deafness and preauricular fistulae developed proteinuria. She had renal insufficiency, and ultrasound revealed bilateral small kidneys. These findings indicated that she had branchio-oto-renal (BOR) syndrome. In the present patient, we identified, by using multiplex ligation-dependent probe amplification (MLPA) analysis, a heterozygous EYA1 gene deletion comprising at least exons 5 to 7. In her parents, we did not detect any deletion in EYA1 by MLPA, so the deletion was a de novo mutation. PCR analysis and sequencing of patient DNA revealed a heterozygous similar to 17 kb EYA1 deletion starting from the eight last bases of exon 4 and proceeding to base 1,217 of intron 7. Furthermore, in place of this deleted region was inserted a 3756-bp-long interspersed nuclear elements-1 (LINE-1, L1). Accordingly, RT-PCR showed that exons 4-7 were not present in EYA1 mRNA expressed from the mutated allele. Although there are reports of L1 element insertion occurring in various human diseases, this is the first report of a large EYA1 deletion in combination with L1 element insertion.
    SPRINGER, Jul. 2010, PEDIATRIC NEPHROLOGY, 25(7) (7), 1343 - 1348, English
    [Refereed]
    Scientific journal

  • Makiko Nakayama, Kandai Nozu, Yuki Goto, Koichi Kamei, Shuichi Ito, Hidenori Sato, Mitsuru Emi, Koichi Nakanishi, Shigeru Tsuchiya, Kazumoto Iijima
    Hepatocyte nuclear factor 1 beta (HNF1 beta) abnormalities have been recognized to cause congenital anomalies of the kidney and urinary tract (CAKUT), predominantly affecting bilateral renal malformations. To further understand the spectrum of HNF1 beta related phenotypes, we performed HNF1B gene mutation and deletion analyses in Japanese patients with renal hypodysplasia (n = 31), unilateral multicystic dysplastic kidney (MCDK; n = 14) and others (n = 5). We identified HNF1B alterations in 5 out of 50 patients (10%). De novo heterozygous complete deletions of HNF1B were found in 3 patients with unilateral MCDK. Two of the patients showed contralateral hypodysplasia, whereas the other patient showed a radiologically normal contralateral kidney with normal renal function. Copy number variation analyses showed 1.4 Mb microdeletions involving the whole HNF1B gene with breakpoints in flanking segmental duplications. We also identified 1 novel truncated mutation (1007insC) and another missense mutation (226G > T) in patients with bilateral hypodysplasia. HNF1B alterations leading to haploinsufficiency affect a diverse spectrum of CAKUT. The existence of a patient with unilateral MCDK with normal renal function might provide genetic insight into the etiology of these substantial populations of only unilateral MCDK. The recurrent microdeletions encompassing HNF1B could have a significant impact on the mechanism of HNF1B deletions.
    SPRINGER, Jun. 2010, PEDIATRIC NEPHROLOGY, 25(6) (6), 1073 - 1079, English
    [Refereed]
    Scientific journal

  • 島 友子, 野津 寛大, 戸川 寛子, 貝藤 裕史, 飯島 一誠, 松尾 雅文, 中西 浩一, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2010, 日本小児腎臓病学会雑誌, 23(1Suppl.) (1Suppl.), 87 - 87, Japanese

  • 島 友子, 中西 浩一, 戸川 寛子, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2010, 日本小児腎臓病学会雑誌, 23(1Suppl.) (1Suppl.), 123 - 123, Japanese

  • 運動後急性腎不全とPRES(Posterior reversible encephalopathy syndrome)の合併を反復した腎性低尿酸血症の1例
    島 友子, 中西 浩一, 戸川 寛子, 野津 寛大, 飯島 一誠, 吉川 徳茂
    日本小児高血圧研究会, Jun. 2010, 小児高血圧研究会誌, 7(1) (1), 64 - 65, Japanese

  • Hideki Kumagai, Shizuko Matsumoto, Kandai Nozu
    We report here the first published case of a pediatric patient with Gitelman's syndrome (GS) in whom hypokalemia-associated rhabdomyolysis developed. A 13-year-old girl was admitted with weakness of the extremities, walking difficulty and calf pain. Laboratory data showed a serum potassium level of 2.1 mmol/l and a serum creatinine phosphokinase level of 1,248 IU/l plus myoglobinemia. The presence of normomagnesemia was the basis for a genetic analysis of the thiazide-sensitive sodium chloride cotransporter gene, which revealed compound heterozygous mutations in this gene. Prompt fluid expansion and potassium supplementation led to regression of the muscle symptoms. Hypokalemia can be a rare cause of rhabdomyolysis in patients with GS, even in childhood. We emphasize that genetic analysis is advisable to determine whether the suspicion of GS is warranted.
    SPRINGER, May 2010, PEDIATRIC NEPHROLOGY, 25(5) (5), 953 - 955, English
    [Refereed]
    Scientific journal

  • X染色体連鎖型Alport症候群の臨床的検討
    橋村 裕也, 野津 寛大, 岡 政史, 忍頂寺 毅史, 貝藤 裕史, 飯島 一誠, 中西 浩一, 吉川 徳茂, 松尾 雅文
    (一社)日本腎臓学会, May 2010, 日本腎臓学会誌, 52(3) (3), 338 - 338, Japanese

  • OKA Masafumi, NOZU Kandai, IIJIMA Kazumoto, MATSUO Masafumi
    Alport syndrome (AS) is a hereditary and progressive glomerular nephritis that is frequently associated with sensorineural hearing loss and less ocular changes. It usually presents in children as haematuria and proteinuria, and progresses to end-stage renal disease (ESRD) increasing with age.
     AS is caused by abnormal type IV collagen which is composed of three α chains complex (α1-α1-α2 and α3-α4-α5, α5-α5-α6). The α3-α4-α5 component is expressed in the glomerular basement membrane (GBM). The α5-α5-α6 component is expressed in the Bowman's capsule but not in the GBM.
     AS is genetically heterogeneous and X-linked (XLAS), with both autosomal recessive (ARAS), and autosomal dominant (ADAS) has been clarified.
     XLAS accounts for approximately 85% of affected AS patients. It is caused by mutations in the COL4A5 gene on the X chromosome. XLAS is reported that 90% of male patients are at risk of developing ESRD before the age of 40, and females typically show milder clinical symptoms, although the probability of developing ESRD before the age of 40 year is 12%.
     ARAS accounts for about 15% of patients with AS. It is caused by homozygous mutations or compound heterozygous mutations in the COL4A3 or COL4A4 genes.
     ARAS usually presents most severe clinical findings. In our study, about 70% of ARAS from eight families) 71.4% of patients had reached ESRD until 15 years old. ARAS is suggested by presence of one or more of following criteria: (i) severe early disease in both females and males; (ii) parental consanguinity; (iii) absence of severe renal disease in the parents. Recently heterozygous mutations in COL4A3 or COL4A4 have been detected in 40% of families with thin basement membrane nephropathy (TBMN). Today understanding of the mode of inheritance for TBMN and ARAS is that heterozygotes with TBMN can be considered carriers for ARAS, and the offspring from a couple in which both parents have TBMN can be expected to get ARAS. We underline that when you examine the patient whose father and mother have histories of TBMN, should rule out ARAS.
     ADAS has been observed in a few families. It is caused by heterozygous mutations in the COL4A3 or COL4A4. Both female and male patients show a high clinical variability with renal phenotypes ranging from isolated haematuria to late onset ESRD. When EM findings show TBMN in young patients, it is not able to distinguish ADAS or TBMN. Immunohistochemical study of renal GBMs shows normal pattern in both ADAS and TBMN. Therefore we need the detailed family histories and to follow up the patients whether decrease renal function or not.
     In conclusion, we described mainly about the autosomal AS. Recently relations between ARAS and TBMN have revealed, AS may be the more frequent disease. It is not revealed what is the difference between ARAS and ADAS in molecular aspects, they have mutations in the same genes of COL4A3 or COL4A4. We will conduct molecular analysis in AS and reveal the mechanism and clinical findings of AS.
    The Japanese Society for Pediatric Nephrology, Apr. 2010, Nihon Shoni Jinzobyo Gakkai Zasshi, 23(1) (1), 8 - 12, Japanese

  • Kazunari Kaneko, Masafumi Hasui, Atsuko Hata, Daisuke Hata, Kandai Nozu
    SPRINGER, Apr. 2010, PEDIATRIC NEPHROLOGY, 25(4) (4), 781 - 782, English
    [Refereed]

  • Kazunari Kaneko, Sachiyo Tanaka, Masafumi Hasui, Kandai Nozu, Rafal Przybyslaw Krol, Kazumoto Iijima, Keisuke Sugimoto, Tsukasa Takemura
    Gene mutations in COL4A5 located on Xq22 are believed to cause X-linked Alport syndrome, whereas mutations in COL4A3 and COL4A4 located on chromosome 2 are associated with autosomal inherited Alport syndrome or benign familial hematuria. A family with benign familial hematuria caused by COL4A5 mutation, implying X-linked transmission, is reported here for the first time. This result suggests that COL4A5 should be added to the list of causative genes for benign familial hematuria, although the mechanism(s) by which the same mutation leads to the distinct phenotypes, i.e. X-linked Alport syndrome or benign familial hematuria, remains unknown.
    SPRINGER, Mar. 2010, PEDIATRIC NEPHROLOGY, 25(3) (3), 545 - 548, English
    [Refereed]
    Scientific journal

  • 常染色体劣性Alport症候群女児例におけるIV型コラーゲンα1～α6鎖染色の検討
    三浦 健一郎, 高橋 和浩, 関根 孝司, 柳澤 敦広, 生井 良幸, 野津 寛大, 岡 政史, 飯島 一誠, 内藤 一郎, 五十嵐 隆
    (公社)日本小児科学会, Feb. 2010, 日本小児科学会雑誌, 114(2) (2), 228 - 228, Japanese

  • Tanaka Sachiyo, Hasui Masafumi, Nozu Kandai, Iijima Kazumoto, Sugimoto Keisuke, Takemura Tsukasa, Kaneko Kazunari
    Japanese Society for Pediatric Nephrology, 2010, Nihon Shoni Jinzobyo Gakkai Zasshi, 23(2) (2), 172 - 178
    Scientific journal

  • Teruo Fujita, Takeshi Shimooka, Yoshie Teraoka, Yoshifumi Sugita, Hiroshi Kaito, Kazumoto Iijima, Masafumi Matsuo, Kandai Nozu, Ryojiro Tanaka
    SPRINGER, Dec. 2009, PEDIATRIC NEPHROLOGY, 24(12) (12), 2467 - 2469, English
    [Refereed]
    Scientific journal

  • KANDA Kyoko, NOZU Kandai, HASHIMURA Yuya, IIJIMA Kazumoto, MATSUO Masafumi
    Pseudohypoaldosteronism type 1 (adPHA1) is a rare inherited condition that is characterized by ranal resistance to aldsterone, with salt wasting, hyperkalemia, and metabolic acidosis. At least two forms of PHA1, autosomal dominant (adPHA1) and recessive forms (arPHA1) of the disease have been descried. In most cases, adPHA1 is caused by mutations of the gene coding human mineralcorticoid receptor (MR), and arPHA1 is caused by genes coding epithelial Na channel (ENaC). AdPHA1 form shares many of the same clinical features as arPHA1, including failure to thrive, salt loss, hyperkalemia, and metabolic acidosis despite elevated aldosterone and plasma renin activity (PRA) levels. However, patients with arPHA1 generally have much severe symptoms than them with adPHA1 patients. Recently, it is reported that the symptoms with PHA1 are similar to those with Bartter syndrome type II. Patients with PHA1 genenrally require oral salt supplementation, but typically show a gradual clinical improvement with regard renal salt loss during childhood.
    The Japanese Society for Pediatric Nephrology, Nov. 2009, Nihon Shoni Jinzobyo Gakkai Zasshi, 22(2) (2), 123 - 125, Japanese

  • TAKEWA Reiko, TANIGUTI Naho, TANAKA Sachiyo, NAKANO Takahide, HASUI Masafumi, KANEKO Kazunari, NOZU Kandai
    Idiopathic renal hypouricemia, mainly caused by a defect in a gene (SLC22A12) encoding the urate transporter (URAT1), is a disorder with an incidence of 0.15% in Japan. Patients exhibit an increase in uric acid excretion due to an isolated defect in renal tubular transport of uric acid and are known to be frequently complicated by an exercise-induced acute renal failure (ARF).
     The mechanisms for development in exercise-induced ARF in patients with idiopathic renal hypouricemia remain unclear while two possible explanations have been proposed: either urate nephropathy results from an increase in urate production during exercise, or renal reperfusion injury due to vasoconstriction results from an exercise- induced increase in oxygen free radicals and a lack of urate, one of the free radical scavengers.
     In this review, we summarized the putative mechanisms regarding the development for exercise-induced ARF in patients with idiopathic renal hypouricemia based on the previous reports. Furthermore, we found the oxidative imbalance after exercise in a patient with idiopathic renal hypouricemia and postulate as a cause for exercise-induced ARF in this condition.
     A 15 year-old-girl with idiopathic renal hypouricemia caused by a mutation in the URAT1 gene (compound heterozygous mutation for R90H/W258X) was referred us for further evaluation of exercise-induced ARF. We therefore studied the oxidative balance during and soon after exercise in this girl to investigate causal relationship between idiopathic renal hypouricemia and exercise-induced ARF, after written informed consent was obtained. As a result, her serum level of reactive oxygen species (ROS) increased with decreasing antioxidant potential capacity soon after the initiation of anaerobic stress due to treadmill exercise. Thereafter, serum levels of ROS and antioxidant potential showed a parallel course, returning to the baseline values at 240 min after exercise.
     Thus, some patients with idiopathic renal hypouricemia demonstrate oxidative imbalance soon after exercise with a predisposition to exercise-induced ARF and we therefore postulate that oxidative imbalance after exercise in a patient with idiopathic renal hypouricemia plays an important role. Antioxidant properties may alter this imbalance by augmenting the antioxidant activity.
    The Japanese Society for Pediatric Nephrology, Nov. 2009, Nihon Shoni Jinzobyo Gakkai Zasshi, 22(2) (2), 147 - 151, Japanese

  • HASHIMURA Yuya, NOZU Kandai, NINCHOJI Takeshi, KAITO Hiroshi, NAKANISHI Koichi, YOSHIKAWA Norishige, IIJIMA Kazumoto, MATSUO Masafumi
    Hemolytic-uremic syndrome (HUS) patients often need treatment with dialysis temporally at the acute phase of HUS and rarely develop chronic renal failure after years of apparent recovery. We report a 14-year-old girl who developed HUS at 3 years of age. She showed acute renal failure and treated with peritoneal dialysis for about a month. She also showed seizure and disturbed consciousness on acute phase. Although her kidney function normalized, and her protenuria was disappeared, high urine β2MG level was persisted. Therefore we performed kidney biopsy, and showed a portion of scarring tissue which findings may derived from the cortical necrosis on acute phase. Because of these findings, we started to treat with ACE inhibitor. After the induction of this treatment, her urine β2MG level was normalized. Eight years after the onset of HUS, she began to showed severe proteinuria and we performed repeated kidney biopsy. It showed focal segmental glomerular sclerosis and severe fibrosis of intestitiums and predicted to have bad renal prognosis. We should follow up HUS patients carefully and need long period observation after the onset of HUS in patients with prolonged renal failure on early phase.
    The Japanese Society for Pediatric Nephrology, Nov. 2009, Nihon Shoni Jinzobyo Gakkai Zasshi, 22(2) (2), 183 - 187, Japanese

  • Kandai Nozu, Kazumoto Iijima, Yoshimi Nozu, Ei Ikegami, Takehide Imai, Xue Jun Fu, Hiroshi Kaito, Koichi Nakanishi, Norishige Yoshikawa, Masafumi Matsuo
    Many mutations have been detected in the SLC12A3 gene of Gitelman syndrome (GS, OMIM 263800) patients. In previous studies, only one mutant allele was detected in similar to 20 to 41% of patients with GS; however, the exact reason for the nonidentification has not been established. In this study, we used RT-PCR using mRNA to investigate for the first time transcript abnormalities caused by deep intronic mutation. Direct sequencing analysis of leukocyte DNA identified one base insertion in exon 6 (c.818_819insG), but no mutation was detected in another allele. We analyzed RNA extracted from leukocytes and urine sediments and detected unknown sequence containing 238bp between exons 13 and 14. The genomic DNA analysis of intron 13 revealed a single-base substitution (c.1670-191C>T) that creates a new donor splice site within the intron resulting in the inclusion of a novel cryptic exon in mRNA. This is the first report of creation of a splice site by a deep intronic single-nucleotide change in GS and the first report to detect the onset mechanism in a patient with GS and missing mutation in one allele. This molecular onset mechanism may partly explain the poor success rate of mutation detection in both alleles of patients with GS. (Pediatr Res 66: 590-593,2009)
    INT PEDIATRIC RESEARCH FOUNDATION, INC, Nov. 2009, PEDIATRIC RESEARCH, 66(5) (5), 590 - 593, English
    [Refereed]
    Scientific journal

  • Kyoko Kanda, Kandai Nozu, Naoki Yokoyama, Ichiro Morioka, Akihiro Miwa, Yuya Hashimura, Hiroshi Kaito, Kazumoto Iijima, Masafumi Matsuo
    Background: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations. Methods and Results: We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. Conclusion: mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.
    BIOMED CENTRAL LTD, Nov. 2009, BMC NEPHROLOGY, 10, 37, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Kazumoto Iijima, Kazuo Kawai, Yoshimi Nozu, Atsushi Nishida, Yasuhiro Takeshima, Xue Jun Fu, Yuya Hashimura, Hiroshi Kaito, Koichi Nakanishi, Norishige Yoshikawa, Masafumi Matsuo
    Type I Bartter syndrome (BS), an inherited salt-losing tubulopathy, is caused by mutations of the SLC12A1 gene. While several intronic nucleotide changes in this gene have been detected, transcriptional analysis had not been conducted because mRNA analysis is possible only when renal biopsy specimens can be obtained or occasionally when mRNA is expressed in the leukocytes. This report concerns a type I BS patient due to compound heterozygosity for the SLC12A1 gene. Genomic DNA sequencing disclosed the presence of two novel heterozygous mutations of c.724 + 4A > G in intron 5 and c.2095delG in intron 16, but it remains to be determined whether the former would be likely to influence the transcription. In this report, we conducted both in vivo assay of RT-PCR analysis using RNA extracted from the proband's urinary sediments and in vitro functional splicing study by minigene construction, and obtained evidence that this intronic mutation leads to complete exon 5 skipping. To the best of our knowledge, this is the first study to use non-invasive methods for both an in vivo assay and an in vitro functional splicing assay of inherited kidney disease. These analytical assays could be adapted for all inherited kidney diseases.
    SPRINGER, Oct. 2009, HUMAN GENETICS, 126(4) (4), 533 - 538, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Rafal Przybyslaw Krol, Koichi Nakanishi, Norishige Yoshikawa, Yoshimi Nozu, Yasufumi Ohtsuka, Kazumoto Iijima, Masafumi Matsuo
    SPRINGER, Sep. 2009, PEDIATRIC NEPHROLOGY, 24(9) (9), 1773 - 1774, English
    [Refereed]

  • 運動後急性腎不全とPRES(Posterior reversible encephalopathy syndrome)の合併を反復した腎性低尿酸血症の1例
    島 友子, 中西 浩一, 戸川 寛子, 野津 寛大, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, Aug. 2009, 日本腎臓学会誌, 51(6) (6), 778 - 778, Japanese

  • 遺伝性腎疾患におけるintron内の変異に伴う病気発症メカニズム解明のための実験系の確立
    野津 寛大, 貝藤 裕史, 橋村 裕也, 忍頂寺 毅史, 飯島 一誠, 松尾 雅文, 中西 浩一, 吉川 徳茂
    (一社)日本腎臓学会, Aug. 2009, 日本腎臓学会誌, 51(6) (6), 794 - 794, Japanese

  • 腎不全に至ったステロイド感受性微小変化型ネフローゼ症候群の1例
    橋村 裕也, 忍頂寺 毅史, 貝藤 裕史, 野津 寛大, 飯島 一誠, 中西 浩一, 吉川 徳茂, 松尾 雅文
    (一社)日本腎臓学会, Aug. 2009, 日本腎臓学会誌, 51(6) (6), 796 - 796, Japanese

  • Koichi Kamei, Shuichi Ito, Kandai Nozu, Shuichiro Fujinaga, Makiko Nakayama, Mayumi Sako, Mari Saito, Maki Yoneko, Kazumoto Iijima
    We conducted a multicenter prospective trial to evaluate the efficacy, safety and pharmacokinetics of a single dose of rituximab (375 mg/m(2) body surface area) for the treatment of children with refractory steroid-dependent nephrotic syndrome (SDNS). All patients (n = 12) were able to discontinue steroids at a median of 74 days after treatment. The frequency of relapses per 6 months was significantly reduced and the steroid-free period per 6 months was significantly increased after treatment compared with those before treatment. The condition in nine of the patients (75%) relapsed at a median of 129 days after treatment, and seven patients were given additional rituximab due to steroid dependency. Most of the relapses developed simultaneously with recovery of B-cells. However, three patients (25%) did not have a relapse with B-cell recovery and the disease was kept in remission for more than 1 year. None of the patients developed life-threatening adverse events. This is the first report of a prospective study of a single dose of rituximab for refractory SDNS. Treatment with a single dose of rituximab may be effective for refractory SDNS, but its efficacy to prevent relapses was transient in most of the patients.
    SPRINGER, Jul. 2009, PEDIATRIC NEPHROLOGY, 24(7) (7), 1321 - 1328, English
    [Refereed]
    Scientific journal

  • 島 友子, 中西 浩一, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 飯島 一誠, 田中 亮二郎, 佐々木 聡, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2009, 日本小児腎臓病学会雑誌, 22(1Suppl.) (1Suppl.), 94 - 94, Japanese

  • IV型コラーゲンα5鎖の発現をモザイク状に認めたAlport症候群の1男児例
    安齋 未知子, 倉山 英昭, 松村 千恵子, 金本 勝義, 飛田 尚美, 北村 博司, 城 謙輔, 野津 寛大
    (公社)日本小児科学会, Jun. 2009, 日本小児科学会雑誌, 113(6) (6), 1028 - 1028, Japanese

  • Yuya Hashimura, Kandai Nozu, Hirokazu Kanegane, Toshio Miyawaki, Akira Hayakawa, Norishige Yoshikawa, Koichi Nakanishi, Minoru Takemoto, Kazumoto Iijima, Masafumi Matsuo
    Several studies have suggested that T cell-producing permeability factors might lead to proteinuria in minimal change nephrotic syndrome (MCNS). However, it is still unclear whether T-cell abnormalities cause MCNS. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulation system, which leads to severe autoimmune phenomena including autoimmune enteropathy, atopic dermatitis with high levels of serum immunoglobulin E (IgE), type 1 diabetes mellitus (T1DM), and severe infection such as sepsis, which frequently result in death within the first 2 years of life. This disease is caused by mutations in the FOXP3 gene that result in the defective development of regulatory T (Treg) cells. This report describes a 5-year-old boy with IPEX syndrome with a 3 bp deletion in the FOXP3 gene (c.748-750delAAG, p.250K.del) and a paucity of CD4(+) CD25(+) FOXP3(+) T cells. The boy's condition was complicated by MCNS in addition to many IPEX-related manifestations, such as atopic dermatitis, T1DM, enteropathy, sepsis and hemolytic anemia. This is the first report of IPEX syndrome complicated by MCNS, and our findings imply that Treg cell dysfunction may be crucial for the development of MCNS.
    SPRINGER, Jun. 2009, PEDIATRIC NEPHROLOGY, 24(6) (6), 1181 - 1186, English
    [Refereed]
    Scientific journal

  • Hiroko Togawa, Koichi Nakanishi, Yuko Shima, Mina Obana, Mayumi Sako, Kandai Nozu, Ryojiro Tanaka, Kazumoto Iijima, Norishige Yoshikawa
    Mast cell-derived chymase is an angiotensin II-forming enzyme that appears to be involved in tubulointerstitial fibrosis in the kidneys. Previous studies have shown that the level of chymase increases in grafted kidneys after rejection and in adult patients with diabetic nephropathy. However, the significance of chymase in children with renal diseases has not been investigated. Using immunohistochemistry, we have investigated chymase expression in biopsy samples of renal tissue from 104 children with kidney diseases, including rapidly progressive crescentic glomerulonephritis (n = 3), diabetic nephropathy (n = 2), allografted kidney (n = 3), membranoproliferative glomerulonephritis (n = 6), immunoglobulin A nephropathy (n = 33) and Henoch-Schonlein purpura nephritis (n = 23). Increased numbers of chymase-positive mast cells were observed in the renal cortex of all three patients with crescentic glomerulonephritis (mean 26.0/mm(2); range 19.3-36.8/mm(2)). Chymase-positive cells were also observed in the renal biopsy of an allografted kidney and in those from children with diabetic nephropathy. The mean number of chymase-positive cells in renal tissue samples characterized by each renal disease was significantly correlated with the mean intensity of the interstitial fibrosis in that same tissue sample (Spearman's rank correlation test p = 0.0013; rank correlation coefficient 0.84). These findings suggest that mast cell-derived chymase plays an important role in juvenile crescentic glomerulonephritis.
    SPRINGER, May 2009, PEDIATRIC NEPHROLOGY, 24(5) (5), 1071 - 1075, English
    [Refereed]
    Scientific journal

  • 重症小児IgA腎症における治療後腎IgA沈着消失の臨床病理学的意義
    島 友子, 中西 浩一, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 飯島 一誠, 田中 亮二郎, 佐々木 聡, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2009, 日本腎臓学会誌, 51(3) (3), 250 - 250, Japanese

  • X染色体連鎖型アルポート症候群(XLAS)の分子遺伝学的検討
    野津 寛大, 貝藤 裕史, 神田 杏子, 橋村 裕也, 飯島 一誠, 松尾 雅文, 中西 浩一, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2009, 日本腎臓学会誌, 51(3) (3), 290 - 290, Japanese

  • Kazunari Kaneko, Naho Taniguchi, Yuko Tanabe, Takahide Nakano, Masafumi Hasui, Kandai Nozu
    An important complication of idiopathic renal hypouricemia is exercise-induced acute renal failure (ARF). The most plausible explanation for this complication is that decreased antioxidant potential leads to kidney injury by reactive oxygen species (ROS). We demonstrated this oxidative imbalance by a concomitant assessment of ROS production and antioxidant system capability in a 15- year-old girl with idiopathic renal hypouricemia caused by a mutation in the urate transporter (URAT1) gene. Her serum level of ROS increased with decreasing antioxidant potential capacity soon after the initiation of anaerobic stress due to treadmill exercise. Thereafter, serum levels of ROS and antioxidant potential showed a parallel course, returning to the baseline values at 240 min after exercise. Some patients with idiopathic renal hypouricemia demonstrate oxidative imbalance soon after exercise with a predisposition to exercise-induced acute renal failure. Antioxidant properties may alter this imbalance by augmenting the antioxidant activity.
    SPRINGER, Apr. 2009, PEDIATRIC NEPHROLOGY, 24(4) (4), 869 - 871, English
    [Refereed]
    Scientific journal

  • Yuko Shima, Koichi Nakanishi, Hiroko Togawa, Mina Obana, Mayumi Sako, Masakazu Miyawaki, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa
    A 6-year-old previously healthy Japanese girl was found to have dipstick 2+ proteinuria and a goiter based on the results of a routine school medical examination. Her serum free-thyroxine level was 4.98 ng/dL (normal range 0.95-1.74 ng/dL), thyroid-stimulating hormone (TSH) was less than 0.003 mu U/mL (0.34-3.88 mu U/mL), anti-microsomal (anti-thyroid-peroxidase) antibody was 1600 T (up to 100), anti-thyroglobulin antibody was 400 T (up to 100), and TSH-receptor antibody was 84% (up to +/- 10%). These results are consistent with a diagnosis of Graves' disease. Electron microscopy examination of a renal biopsy specimen revealed electron-dense deposits located in the subepithelial spaces, and immunofluorescence microscopy examination demonstrated bright granular stainings of immunoglobulin G along the glomerular capillary walls. These findings are characteristic of membranous nephropathy. To investigate the relationship between the membranous nephropathy and Graves' disease, we carried out a second immunofluorescence study, which revealed that the immunoglobulin G granular deposits corresponded to glomerular granular staining of thyroid-peroxidase, whereas staining for thyroglobulin was absent. It was therefore assumed that the deposition of immune complexes mediated by thyroid-peroxidase had caused the membranous nephropathy in this patient. This is the first report of membranous nephropathy associated with Graves' disease in which deposits of thyroid-peroxidase, rather than thyroglobulin, have been confirmed in the kidney.
    SPRINGER, Mar. 2009, PEDIATRIC NEPHROLOGY, 24(3) (3), 605 - 608, English
    [Refereed]
    Scientific journal

  • X染色体連鎖型アルポート症候群の分子遺伝学的検討
    野津 寛大, Krol Rafal, 神田 杏子, 橋村 裕也, 中西 浩一, 吉川 徳茂, 飯島 一誠, 松尾 雅文
    (公社)日本小児科学会, Feb. 2009, 日本小児科学会雑誌, 113(2) (2), 296 - 296, Japanese

  • Hajime Yamazaki, Kandai Nozu, Ichiei Narita, Michio Nagata, Yoshimi Nozu, Xue Jun Fu, Masafumi Matsuo, Kazumoto Iijima, Fumitake Gejyo
    Type I Bartter syndrome (BS) is caused by mutations of the Na-K-2Cl cotransporter (NKCC2)-encoding SLC12A1 gene. The clinical phenotype of this severe form of BS is characterized by polyhydramnios, premature delivery, failure to thrive, and nephrocalcinosis, and the diagnosis is usually made during the antenatal-neonatal period. This report concerns a 29-year-old Japanese man with atypical type I BS due to a compound heterozygous mutation of the SLC12A1 gene. He was born after full-term pregnancy complicated by polyhydramnios. He first presented with asymptomatic proteinuria at the age of 20 years and was diagnosed with BS based on laboratory data. There were signs of moderate proteinuria, mild renal dysfunction and nephrocalcinosis. Renal biopsy showed focal segmental glomerulosclerosis (FSGS), and genetic testing revealed novel mutations of A555V and G809V in the SLC12A1 gene. The patient's sister showed the same clinical course, laboratory test abnormalities and gene mutations. Our patient had a type I BS with an atypical clinical course, which was diagnosed when he was 20 years old. Laboratory findings indicated phenotypic variability in this disease, and the presence of nephropathy suggested that FSGS might be one of the lesions causing end-stage renal failure in this disease
    SPRINGER, Feb. 2009, PEDIATRIC NEPHROLOGY, 24(2) (2), 415 - 418, English
    [Refereed]
    Scientific journal

  • 神田 杏子, 野津 寛大, 貝藤 裕史, 松尾 雅文, 亀井 宏一, 飯島 一誠, 中西 浩一, 吉川 徳茂, 関根 孝司, 五十嵐 隆, 小松 博史, 宮下 律子
    (一社)日本小児腎臓病学会, Nov. 2008, 日本小児腎臓病学会雑誌, 21(2) (2), 234 - 234, Japanese

  • 野津 寛大, Krol Rafal, 貝藤 裕史, 神田 杏子, 橋村 裕也, 松尾 雅文, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2008, 日本小児腎臓病学会雑誌, 21(2) (2), 235 - 235, Japanese

  • Kandai Nozu, Rafal Przybyslaw Krol, Yasufumi Ohtsuka, Koichi Nakanishi, Norishige Yoshikawa, Yoshimi Nozu, Hiroshi Kaito, Kyoko Kanda, Yuya Hashimura, Yuhei Hamasaki, Kazumoto Iijima, Masafumi Matsuo
    Alport syndrome is the most common form of hereditary nephritis, and the majority of cases are caused by mutations in the COL4A5 gene. However, direct sequencing by polymerase chain reaction (PCR), from genomic DNA, or reverse transcriptase-polymerase chain reaction (RT-PCR), from mRNA, or polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) has reportedly resulted in detection rates of 31% to 84%, but of only 20% to 71% when restricted to female patients. This report concerns two female patients with X-linked Alport syndrome. Although mutational analysis of the COL4A5 gene was conducted with direct sequencing using genomic DNA and mRNA extracted from leukocytes, the results were negative for detection of mutations. Semi-quantitative PCR using genomic DNA was therefore conducted to detect large heterozygous deletions. The results were that the first patient showed complete loss of the COL4A5 gene and the second patient showed deletion from exons 37 to 51. Our patients possessed large heterozygous deletions in the COL4A5 gene that could not be detected with the standard direct sequencing method and were identified with semi-quantitative PCR. Previously reported mutation detection rates for female patients have been lower than overall rates. Our findings indicate that this difference may, in part, be due to failure to detect this type of mutation with conventional analytical methods.
    SPRINGER, Nov. 2008, PEDIATRIC NEPHROLOGY, 23(11) (11), 2085 - 2090, English
    [Refereed]
    Scientific journal

  • Rafal Przybyslaw Krol, Kandai Nozu, Koichi Nakanishi, Kazumoto Iijima, Yasuhiro Takeshima, Xue Jun Fu, Yoshimi Nozu, Hiroshi Kaito, Kyoko Kanda, Masafumi Matsuo, Norishige Yoshikawa
    Background. Alport syndrome is the most common form of hereditary nephritis and is mainly caused by mutations in the COL4A5 gene, which shows the X-linked form. It is well known that some male Alport syndrome cases show a relatively mild phenotype, but few molecular investigations have been conducted to clarify the mechanism of this phenotype. Methods and results. This report concerns an 8-year-old male sporadic Alport syndrome patient. While electron microscopy of the glomerular basement membrane showed typical findings for Alport syndrome, however, the immunohistochemical analysis of the glomerulus showed mosaic staining of the type IV collagen alpha 5 chain. The mutational analysis of the COL4A5 gene unexpectedly disclosed two peaks at the intron 43 splicing acceptor site (c. 3998-2 a/t) with direct sequencing. Restriction enzyme analysis demonstrated that the presence of somatic mosaicism was responsible for this mutation. mRNA extracted from the urinary sediments was analysed by RT-PCR and two PCR fragments were amplified, one consisting of a normal sequence and one with skipping of exon 44. Conclusions. Our findings indicate that somatic mosaicism for COL4A5 is responsible for male X-linked Alport syndrome with an alpha 5 mosaic staining pattern. Several cases with somatic mosaicism have previously been reported, however, this is the first case where the presence of this mutation was proved with a comprehensive analysis of genomic DNA, mRNA and alpha 5 expression in the tissues. Somatic mosaicism may thus be one of the causes of the mild phenotype in Alport syndrome.
    OXFORD UNIV PRESS, Aug. 2008, NEPHROLOGY DIALYSIS TRANSPLANTATION, 23(8) (8), 2525 - 2530, English
    [Refereed]
    Scientific journal

  • 貝藤 裕史, 野津 寛大, 神田 杏子, 田中 亮二郎, 吉矢 邦彦, 金 鐘一, 飯島 一誠, 吉川 徳茂, 兵頭 洋二, 石村 武志, 竹田 雅, 藤澤 正人, 松尾 雅文
    末期腎不全(ESRD)に至り腎移植を行った小児ネフローゼ症候群の4症例を経験した。いずれもステロイド抵抗性ネフローゼ症候群を発症し、腹膜透析等を行うもESRDに至り母親をドナーに血液型適合生体腎移植が行なわれた。症例1(発症時1歳6ヵ月女児)。腎生検では微小変化で、2歳6ヵ月時に腎移植が施行されたが、原病再発や急性拒絶反応で移植腎を摘出し、現在7歳で血液透析中である。症例2(発症時9歳男児)。腎生検で巣状分節性糸球体硬化症(FSGS)と診断され、12歳時に腎移植が行なわれた。その移植後、リンパ球増殖性疾患(PTLD)が発症したが、現在はPTLD再発は認められていない。症例3(発症時6歳男児)。腎生検でFSGSと診断され、16歳時にESRDで腎移植が行なわれた。以後、サイトメガロウイルス(CMV)感染が認められたが、現在では腎機能は良好である。症例4(発症時3歳男児)。腎生検でFSGSと診断され、16歳時よりESFDに移行し、18歳時に腎移植が行なわれた。目下、1年5ヵ月経過で再発や合併症もなく、腎機能は良好である。
    日本小児腎不全学会, Aug. 2008, 日本小児腎不全学会雑誌, 28, 151 - 153, Japanese

  • Ichiro Kamioka, Kunihiko Yoshiya, Kenichi Satomura, Hiroshi Kaito, Teruo Fujita, Kazumoto Iijima, Koichi Nakanishi, Norishige Yoshikawa, Kandai Nozu, Masafumi Matsuo
    Background : Hemolytic uremic syndrome (HUS) is characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Cases accompanied by prodromal gastrointestinal tract symptoms are referred to as typical HUS. Some severe HUS patients require dialysis or develop central nervous system (CNS) disorders after the onset of HUS. Methods: Patients who developed typical HUS in 2001 and 2002 in Japan, 127 in all, were the study subjects. To identify the risk factors for the development of a severe clinical course, clinical and laboratory data were analyzed on logistic regression. Results: Two of the 127 patients died (1.6%): one from acute cardiac failure and the other from a CNS disorder. Thirty-five patients required dialysis (28%) and 30 had CNS symptoms (24%). Multivariate analysis indicated that the risk factors for need for dialysis were serum sodium and alanine aminotransferase (ALT) levels of <= 130 mEq/L and >= 70 IU/L, respectively, at the onset of HUS and those for developing CNS disorders were dialysis and C-reactive protein (CRP) >= 5.0 mg/dL at the onset of HUS. Conclusions: Because patients with these risk factors, such as low serum sodium, high ALT or high CRP levels, may require dialysis or develop CNS disorders, they should be treated carefully in the early stage of HUS.
    WILEY-BLACKWELL, Aug. 2008, PEDIATRICS INTERNATIONAL, 50(4) (4), 441 - 446, English
    [Refereed]
    Scientific journal

  • Keiji Iida, Kandai Nozu, Yataka Takahashi, Yasuhiko Okimura, Hidesuke Kaji, Masafumi Matsuo, Kazuo Chihara
    W B SAUNDERS CO-ELSEVIER INC, Jun. 2008, AMERICAN JOURNAL OF KIDNEY DISEASES, 51(6) (6), 1077 - 1078, English
    [Refereed]

  • Nahoko Yata, Koichi Nakanishi, Yuko Shima, Hiroko Togawa, Mina Obana, Mayumi Sako, Kandai Nozu, Ryojiro Tanaka, Kazumoto Iijima, Norishige Yoshikawa
    Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976-1989 and 1990-2004. Actuarial survivals were calculated by Kaplan-Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990-2004 period was significantly better than that in 1976-1989 (p=0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p=0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N.
    SPRINGER, Jun. 2008, PEDIATRIC NEPHROLOGY, 23(6) (6), 905 - 912, English
    [Refereed]
    Scientific journal

  • 島 友子, 中西 浩一, 渋田 昌一, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 貝藤 裕史, 吉川 徳茂
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 130 - 130, Japanese

  • 島 友子, 中西 浩一, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 田中 亮二郎, 佐々木 聡, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 171 - 171, Japanese

  • 神田 杏子, 野津 寛大, 貝藤 裕史, 松尾 雅文, 亀井 宏一, 飯島 一誠, 中西 浩一, 吉川 徳茂, 関根 孝司, 五十嵐 隆, 小松 博史, 宮下 律子
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 194 - 194, Japanese

  • 発端者のCOL4A5遺伝子に体細胞モザイクに変異を有し、軽症の臨床症状を示したAlport症候群の2家系
    野津 寛大, 貝藤 裕史, 神田 杏子, 松尾 雅文, 島 友子, 戸川 寛子, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 197 - 197, Japanese

  • X染色体連鎖型アルポート症候群の分子遺伝学的検討
    野津 寛大, Krol Rafal, 貝藤 裕史, 神田 杏子, 橋村 裕也, 松尾 雅文, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 197 - 197, Japanese

  • 貝藤 裕史, 野津 寛大, 飯島 一誠, 中西 浩一, 太田 和秀, 藤枝 幹也, 由良 和夫, 亀井 宏一, 横山 忠史, 石原 正行, 島 友子, 神田 杏子, 吉川 徳茂, 松尾 雅文
    (一社)日本小児腎臓病学会, May 2008, 日本小児腎臓病学会雑誌, 21(1Suppl.) (1Suppl.), 131 - 131, Japanese

  • 小児腎疾患におけるchymaseの発現
    戸川 寛子, 中西 浩一, 島 友子, 尾鼻 美奈, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2008, 日本腎臓学会誌, 50(3) (3), 363 - 363, Japanese

  • 小手術後の一過性血漿抗利尿ホルモン分泌亢進に関する研究
    神田 杏子, 野津 寛大, 貝藤 裕史, 松尾 雅文, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2008, 日本腎臓学会誌, 50(3) (3), 367 - 367, Japanese

  • Makiko Nakayama, Koichi Kamei, Kandai Nozu, Kentaro Matsuoka, Atsuko Nakagawa, Mayumi Sako, Kazumoto Iijima
    We present the cases of two children with steroid-resistant nephrotic syndrome (SRNS) who were treated with rituximab (anti-CD20 monoclonal antibody). Both were resistant to conventional therapy, and renal biopsy showed focal segmental glomerulosclerosis (FSGS). Combination therapy with methylprednisolone pulse therapy and plasmapheresis was the only way to decrease proteinuria. However, the patients suffered severe reactions to steroid treatment. We therefore treated them with rituximab in a single dose of 375 mg/m(2), which resulted in the rapid clearing of circulating CD19-positive B cells. One month after rituximab treatment, both achieved partial remission; one patient has maintained complete remission for 8 months, and the other relapsed 8 months after the first rituximab treatment with the recovery of peripheral B-cell counts and received a second rituximab treatment. She achieved complete remission 5 months after the second course and has maintained the remission for 2 months. We conclude that rituximab may be an effective treatment for refractory SRNS with FSGS.
    SPRINGER, Mar. 2008, PEDIATRIC NEPHROLOGY, 23(3) (3), 481 - 485, English
    [Refereed]
    Scientific journal

  • K. Nozu, T. Inagaki, X. J. Fu, Y. Nozu, H. Kaito, K. Kanda, T. Sekine, T. Igarashi, K. Nakanishi, N. Yoshikawa, K. Iijima, M. Matsuo
    Background: Bartter syndrome (BS) is a genetic disorder accompanied by hypokalaemic metabolic alkalosis. BS with sensorineural deafness (SND, OMIM602522) is a newly identified phenotype caused by mutations in the BSND gene that encodes barttin, a beta-subunit for chloride channel ClC-Ka and ClC-Kb and classified as type IV BS. Type IV BS features the most severe phenotype entailing life-threatening neonatal volume depletion and chronic renal failure developing during infancy. A recent report described a case of BS with SND from a consanguineous family who showed homozygous mutations in the CLCNKA and CLCNKB genes. This case indicated the possibility of the occurrence of digenic inheritance in BS with SND resulting from double mutations in the CLCNKA and CLCNKB genes. Subject and results: The current report concerns a 2year-old girl from a non-consanguineous family with BS accompanied by SND. In our case, four loss-of-function mutations, consisting of mutations in both parental alleles in both CLCNKA and CLCNKB, were identified. The paternal allele had a nonsense mutation (Q260X) in CLCNKA and a splicing site mutation (IVS17+1 g > a) in CLCNKB. The maternal allele had a large deletion mutation (about 12 kbp) extending from CLCNKA to CLCNKB. Our case provides clear evidence that loss-of-function alleles in both alleles of both CLCNKA and CLCNKB results in a phenotype indistinguishable from that of mutations in BSND (type IV BS). Conclusions: Recent advances in genetics have resulted in a better understanding of many human inherited diseases, but most of them are monogenic disorders and more complex inheritance patterns remain unresolved. Our case provides clear evidence of digenic inheritance outside the scope of Mendelian inheritance disorders.
    B M J PUBLISHING GROUP, Mar. 2008, JOURNAL OF MEDICAL GENETICS, 45(3) (3), 182 - 186, English
    Scientific journal

  • LDL吸着療法(LDL-A)が有効であった巣状分節性糸球体硬化症(FSGS)の1例
    貝藤 裕史, 野津 寛大, 神田 杏子, 吉川 徳茂, 松尾 雅文
    (公社)日本小児科学会, Jan. 2008, 日本小児科学会雑誌, 112(1) (1), 80 - 80, Japanese

  • Tsutomu Nakamura, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa, Yuka Moriya, Motohiro Yamamori, Asae Kako, Masafumi Matsuo, Aki Sakurai, Noboru Okamura, Toshihisa Ishikawa, Katsuhiko Okumura, Toshiyuki Sakaeda
    Cyclosporine (CsA)-induced nephrotoxicity can become a major obstacle to continuous use. The aim of this study was to optimize CsA dose to avoid its irreversible nephrotoxicity. Twenty-three Japanese patients with pediatric-onset systemic lupus erythematosus or idiopathic nephrotic syndrome, who were maintained in a stable condition by oral dosing of CsA microemulsion, were enrolled in this study. The patients were stratified into 3 groups; those with no, reversible, and irreversible nephrotoxicity, according to periodically performed renal pathohistological examinations. A higher concentration of CsA in blood (p=0.002-0.011) and a longer duration of CsA treatment (p=0.002) were risk factors for irreversible nephrotoxicity, and the cumulative CsA dose, the product of the maintenance dose and duration of CsA treatment, was predictive of nephrotoxicity (p=0.036). The maximum target blood concentration at 2 h post-dose, C-2, to avoid CsA-induced irreversible nephrotoxicity was 700 ng/ml, although the cumulative CsA dose of 4850 mg/kg would result in a 50% probability of nephrotoxicity.
    PHARMACEUTICAL SOC JAPAN, Dec. 2007, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 30(12) (12), 2371 - 2375, English
    [Refereed]
    Scientific journal

  • 神田 杏子, 野津 寛大, 貝藤 裕史, 松尾 雅文, 中西 浩一, 吉川 徳茂, 飯島 一誠
    医原性低ナトリウム血症は発生頻度も高く、重篤な中枢神経症状を引き起こす合併症として近年注目を集めている。医原性低ナトリウム血症発症のリスクとして、低張性輸液および高ADH血症が知られている。重篤な感染症罹患時や手術後ではADHの分泌亢進が起こることが知られているが、その他、一般診療でよく見られるような軽症疾患であってもADHの分泌が亢進している危険性があるという報告が散見されており、その際の低張性輸液には注意が必要である。一方、術後嘔気嘔吐症は手術後の合併症として、発症頻度が高く、また、患者に強い不快感を与えるため問題視されている。その予防法や治療法に関しては研究が進められているが、発症機序に関しては未だ不明な点が多い。今回、私たちが経験した腎生検後に低ナトリウム血症および術後嘔気嘔吐症を発症した症例をもとに、これらの合併症の発症機序およびADHの関与につき考察を行った。(著者抄録)
    (一社)日本小児腎臓病学会, Nov. 2007, 日本小児腎臓病学会雑誌, 20(2) (2), 164 - 167, Japanese

  • 日本人3型Bartter症候群患者5例における遺伝子型および表現型に関する研究
    野津 寛大, 貝藤 裕史, 神田 杏子, 松尾 雅文, 中西 浩一, 吉川 徳茂, 上辻 秀和, 神田 祥一郎, 林 良樹, 志水 信彦, 里村 憲一, 飯島 一誠
    3型Bartter症候群は太いヘンレループに存在するクロライドチャネルClC-Kbをコードする遺伝子、CLCNKBの異常で発症することがすでに明らかとなっている。しかし、同疾患においては遺伝子解析の結果、ヘテロ接合体変異しか検出できない症例が多数あることが報告されている。また、同疾患は、Gitelman症候群の特徴とされている低カルシウム尿症および低マグネシウム血症を伴い、Gitelman症候群と診断されている可能性が指摘されている。今回、私たちは日本人3型Bartter症候群患者において、その遺伝学的特徴および臨床的特徴を明らかにしたので報告する。(著者抄録)
    (一社)日本小児腎臓病学会, Nov. 2007, 日本小児腎臓病学会雑誌, 20(2) (2), 152 - 158, Japanese
    [Refereed]

  • 日本人3型Bartter症候群患者5例における遺伝子型および表現型に関する研究
    野津 寛大, 貝藤 裕史, 神田 杏子, 中西 浩一, 吉川 徳茂, 上辻 秀和, 神田 祥一郎, 林 良樹, 志水 信彦, 里村 憲一, 飯島 一誠, 松尾 雅文
    (一社)日本小児腎臓病学会, Nov. 2007, 日本小児腎臓病学会雑誌, 20(2) (2), 235 - 235, Japanese
    [Refereed]

  • Teruo Fujita, Kandai Nozu, Kazumoto Iijima, Ichiro Kamioka, Hiroshi Kaito, Ryojiro Tanaka, Koichi Nakanishi, Masafumi Matsuo, Norishige Yoshikawa
    This report concerns a 9-year-old boy who was diagnosed with atypical type II membranoproliferative glomerulonephritis and later proved to have juvenile acute nonproliferative glomerulitis (JANG). To the best of our knowledge, this is the first report on the long-term clinical and pathological follow-up of JANG.
    SPRINGER, Nov. 2007, PEDIATRIC NEPHROLOGY, 22(11) (11), 1957 - 1961, English
    [Refereed]
    Scientific journal

  • Nozu Kandai
    Nov. 2007, 日本小児腎臓病学会雑誌, 20巻, 2号, pp. 101-104, Japanese
    [Refereed]
    Scientific journal

  • Kandai Nozu, Xue Jun Fu, Koichi Nakanishi, Norishige Yoshikawa, Hiroshi Kaito, Kyoko Kanda, Rafal Przybyslaw Krol, Ritsuko Miyashita, Hidekazu Kamitsuji, Shoichiro Kanda, Yoshiki Hayashi, Kenichi Satomura, Nobuhiko Shimizu, Kazumoto Iijima, Masafumi Matsuo
    Type III Bartter syndrome (BS) (OMIM607364) is caused by mutations in the basolateral chloride channel CIC-Kb gene (CLCNKB). The CLCNKB gene is sometimes reported as having a large deletion mutation, but all cases reported previously were large homozygous deletions and a large heterozygous deletion is impossible to detect by direct sequencing. This report concerns a genetic analysis of five Japanese patients with type III BS. To identify the mutations, we used polymerase chain reaction (PCR) and direct sequencing. To detect large heterozygous deletion mutations of the CLCNKB gene, we conducted semiquantitative PCR amplification using capillary electrophoresis. The result was that four mutations were identified, comprising one novel 2-bp deletion mutation, an entire heterozygous deletion, and a heterozygous deletion mutation of exons 1 and 2. The nonsense mutation W610X was detected in all patients, and this mutation is likely to constitute a founder effect in Japan. Capillary electrophoresis is a new method and extremely useful for detecting large heterozygous deletions, and should be used to examine type III BS cases in whom only a heterozygous mutation has been detected by direct sequencing. This is the first report to identify large heterozygous deletion mutations in the CLCNKB gene in patients with type III BS.
    INT PEDIATRIC RESEARCH FOUNDATION, INC, Sep. 2007, PEDIATRIC RESEARCH, 62(3) (3), 364 - 369, English
    [Refereed]
    Scientific journal

  • Kandai Nozu, Xue Jun Fu, Hiroshi Kaito, Kyoko Kanda, Naoki Yokoyama, Rafal Przybyslaw Krol, Toshihiro Nakajima, Mizutaka Kajiyama, Kazumoto Iijima, Masafumi Matsuo
    Bartter syndrome (BS) is a genetic disorder with hypokalemic metabolic alkalosis and is classified into five types. One of these, type II BS (OMIM 241200), is classified as neonatal Bartter syndrome, which is caused by mutations in the KCNJ1 gene. Transient hyperkalemia and hyponatremia are usually noted in the early postnatal period, but as type II BS is a relatively rare disease, its exact clinical course and genetic background have not yet been thoroughly characterized. This report concerns a male type II BS patient with a novel mutation in the KCNJ1 gene. The unique clinical findings of this case are that hyperkalemia (8.9 mEq/l), hyponatremia, and metabolic acidosis detected in the early postnatal period led to a diagnosis of pseudohypoaldosteronism (PHA). As an adolescent, however, the patient currently shows normal potassium levels and normal renal function, although with hypercalciuria and nephrocalcinosis, without having received any treatment. In such cases, KCNJ1 mutations should be suspected. In our case, genetic analysis of the KCNJ1 gene identified a novel homozygous 1-bp deletion mutation (c.607 del. C in exon 5).
    SPRINGER, Aug. 2007, PEDIATRIC NEPHROLOGY, 22(8) (8), 1219 - 1223, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 常染色体劣性多発性嚢胞腎(ARPKD)の2例の臨床経過の検討
    Nozu Kandai
    Aug. 2007, 日本小児腎不全学会雑誌, 27巻, , pp. 60-62, Japanese
    [Refereed]
    Scientific journal

  • Takashi Sekine, Kandai Nozu, Rashmi Iyengar, Xue Jun Fu, Masafumi Matsuo, Ryojiro Tanaka, Kazumoto Iijima, Emiko Matsui, Yutaka Harita, Jun Inatomi, Takashi Igarashi
    Three distinct OCRL1 mutations in three patients with the Dent disease phenotype are described. All the patients manifested an extremely high degree of low-molecular-weight proteinuria and showed no ocular abnormalities or apparent mental retardation. Urinalysis and blood chemistry showed no findings suggestive of Fanconi syndrome with renal tubular acidosis. Mutations in CLCN5 were ruled out. The mutations identified in OCRL1 are one frame-shift mutation (I127stop) and two missense mutations (R301C and R476W). R301C and R476W mutations might be hot spots in OCRL1, which develop very similar phenotypes as Dent-2.
    SPRINGER, Jul. 2007, PEDIATRIC NEPHROLOGY, 22(7) (7), 975 - 980, English
    [Refereed]
    Scientific journal

  • ベロ毒素産生型腸管出血性大腸菌性溶血性尿毒症症候群におけるMDR1遺伝子多型の関与
    戸川 寛子, 中西 浩一, 島 友子, 尾鼻 美奈, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2007, 日本小児腎臓病学会雑誌, 20(1Suppl.) (1Suppl.), 93 - 93, Japanese

  • 小手術後の一過性血漿抗利尿ホルモン分泌亢進に関する研究 医原性低ナトリウム血症および術後嘔気嘔吐症発症機序に関する考察
    神田 杏子, 野津 寛大, 貝藤 裕史, 松尾 雅文, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2007, 日本小児腎臓病学会雑誌, 20(1Suppl.) (1Suppl.), 112 - 112, Japanese

  • 日本人3型Bartter症候群患者5例における遺伝子型および表現型に関する研究
    野津 寛大, 貝藤 裕史, 神田 杏子, 中西 浩一, 吉川 徳茂, 上辻 秀和, 神田 祥一郎, 林 良樹, 志水 信彦, 里村 憲一, 飯島 一誠, 松尾 雅文
    (一社)日本小児腎臓病学会, Jun. 2007, 日本小児腎臓病学会雑誌, 20(1Suppl.) (1Suppl.), 114 - 114, Japanese
    [Refereed]

  • 血管性紫斑病における腎炎発症とintercellular adhesion molecule-1(ICAM-1)遺伝子多型K469Eの関与
    中西 浩一, 崎山 美知代, 島 友子, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2007, 日本腎臓学会誌, 49(3) (3), 244 - 244, Japanese

  • Nozu Kandai
    Apr. 2007, 日本小児腎臓病学会雑誌, 20巻, 1号, pp. 35-37, Japanese
    [Refereed]
    Scientific journal

  • Ichiro Kamioka, Kandai Nozu, Teruo Fujita, Hiroshi Kaito, Ryojiro Tanaka, Kunihiko Yoshiya, Kazumoto Iijima, Koichi Nakanishi, Norishige Yoshikawa, Masafumi Matsuo
    Background: The three major signs of hemolytic uremic syndrome (HUS) are hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into Shiga toxin-mediated HUS (Stx-HUS) and non-Shiga toxin-mediated HUS (nStx-HUS). The prognosis of nStx-HUS is reported to be less favorable than that of Stx-HUS. Although the association between the prognosis and pathological characteristics of HUS have been reported such that the prognosis was considered to be poor for thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and dependent on the extent of necrosis in cases of renal cortical necrosis, it is not yet clear whether pathological findings are also related to the renal prognosis of nStx-HUS cases. Therefore the purpose of the present paper was to analyze renal biopsy findings and prognosis for five children with nStx-HUS. Methods: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed HUS were reviewed, and information and data were summarized. Results: Histological examination of the kidney led to the diagnosis of arterial TMA in three cases, and glomerular TMA and severe renal cortical necrosis in one case each. Analysis of the relationship between renal histological findings and the prognosis found that three patients with arterial TMA and one patient with severe renal cortical necrosis later developed end-stage renal failure while one patient with glomerular TMA has continued to show normal renal function. Conclusions: These findings indicate that pathological findings are closely related to the prognosis in cases of nStx-HUS.
    BLACKWELL PUBLISHING, Apr. 2007, PEDIATRICS INTERNATIONAL, 49(2) (2), 196 - 201, English
    [Refereed]
    Scientific journal

  • Hiroshi Kaito, Kandai Nozu, Xue J. Fu, Ichiro Kamioka, Teruo Fujita, Kyoko Kanda, Rafal P. Krol, Ryo Suminaga, Akihito Ishida, Kazumoto Iijima, Masafumi Matsuo
    To date, many mutations, including intronic nucleotide changes, in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT) have been reported in Gitelman's syndrome (GS) patients. However, it has not been clarified whether intronic nucleotide changes affect mRNA content. Since mRNA analysis is possible only after obtaining renal biopsy specimens, no studies have been conducted to identify transcript abnormalities in GS. In the study reported here, we investigated such transcript abnormalities for the first time by using mRNA expressed in a patient's urinary sediment cells. Direct sequencing analysis of leukocyte DNA disclosed one known missense mutation (R399C) and one known nucleotide change of the splicing acceptor site of intron 13 (1670-1 g > 1). mRNA extracted from the urinary sediment cells was analyzed by RT-PCR to determine the pathogenic role of the intron mutation. A fragment encompassing exon 13 to 15 was amplified as two products, one consisting of all three exons and the other lacking only exon 14 in its entirety. Our investigation was the first to demonstrate exon 14 skipping in an NCCT transcript in renal cells. This methodology thus constitutes a potential noninvasive analytical tool for every inherited kidney disease.
    INT PEDIATRIC RESEARCH FOUNDATION, INC, Apr. 2007, PEDIATRIC RESEARCH, 61(4) (4), 502 - 505, English
    [Refereed]
    Scientific journal

  • Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Koichi Nakanishi, Kunihiko Yoshiya, Kyoko Kanda, Rafal Przybyslaw Krol, Norishige Yoshikawa, Masafumi Matsuo
    Recent studies indicate that adding the mineralocorticoid receptor antagonist spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI and angiotensin receptor blocker (ARB), which is known as a triple blockade, enhances the more beneficial effects on urinary protein excretion of patients with chronic kidney diseases. In this study, we explored the effects of SP on urinary protein excretion in patients with Alport syndrome featuring persistent proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and ARB (candesartan). Five patients with Alport syndrome were enrolled and SP treatment (25 mg/day) was started. At the start of SP administration, all patients showed good renal function and none of them suffered from hypertension. We decided to assess the effect of SP by determining the morning urinary protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR). After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and 18 months, while EGFR did not change. The drop in systolic and diastolic blood pressure was statistically significant and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (> 5.0 mEq/l). These results suggest that aldosterone receptor blockade combined with ACEI and ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome as in those with other chronic kidney diseases. SP can thus be expected to constitute a good renoprotective agent for Alport syndrome. These preliminary data indicate that large-scale trials of this therapy should be done.
    SPRINGER, Dec. 2006, PEDIATRIC NEPHROLOGY, 21(12) (12), 1824 - 1829, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Akiko Kitamura, Hiroyasu Tsukaguchi, Kazumoto Iijima, Jungo Araki, Motoshi Hattori, Masahiro Ikeda, Masataka Honda, Kandai Nozu, Hitoshi Nakazato, Norishige Yoshikawa, Shoji Kagami, Masaaki Muramatsu, Yong Choi, Hae Il Cheong, Toshio Doi
    OXFORD UNIV PRESS, Nov. 2006, NEPHROLOGY DIALYSIS TRANSPLANTATION, 21(11) (11), 3133 - 3138, English
    [Refereed]
    Scientific journal

  • Xue Jun Fu, Kandai Nozu, Katsumi Goji, Kazushige Ikeda, Ichiro Kamioka, Teruo Fujita, Hiroshi Kaito, Hisahide Nishio, Kazumoto Iijima, Masafumi Matsuo
    OXFORD UNIV PRESS, Oct. 2006, NEPHROLOGY DIALYSIS TRANSPLANTATION, 21(10) (10), 2959 - 2962, English
    [Refereed]
    Scientific journal

  • ハプロタイプ解析と直接シークエンス法にて新たなPKHD1遺伝子変異を同定したARPKDの1例
    Nozu Kandai
    Aug. 2006, 日本小児腎不全学会雑誌, 26巻, , pp. 175-177, 175 - 177, Japanese
    [Refereed]
    Scientific journal

  • Rituximabの投与がFSGSの移植後再発に対し有効であったと考えられた1例 ネフローゼ症候群に対するBリンパ球活性化の関与に関する考察
    Nozu Kandai
    Aug. 2006, 日本小児腎不全学会雑誌, 26巻, , pp. 262-264, 262 - 264, Japanese
    [Refereed]
    Scientific journal

  • Obana M, Nakanishi K, Sako M, Yata N, Nozu K, Tanaka R, Iijima K, Yoshikawa N
    Generally, idiopathic membranous glomerulonephritis (MGN) is a global glomerular disease that affects the whole of the glomerulus. However, idiopathic segmental MGN (SMGN) that shows IgG deposits in a portion of the glomerulus is encountered often. For clarification of whether SMGN is the same entity as idiopathic global MGN (GMGN), the two diseases were compared. From 1978 to 2004, 38 children (11 with SMGN and 27 with GMGN) received a diagnosis of idiopathic MGN. Immunofluorescence microscopy showed segmental granular IgG staining along the capillary loops in SMGN, whereas GMGN showed global staining. On light microscopy, SMGN showed segmental thickening of the glomerular basement membrane, with spike formation, whereas GMGN showed global lesions. The frequency of C1q deposits in SMGN was significantly higher than that in GMGN (91 versus 41%; P < 0.01). On electron microscopy, mesangial electron-dense deposits were detected in 10 (91%) cases of SMGN and also were found in the subepithelial and intramembranous area, whereas only six (22%) cases of GMGN had mesangial electron-dense deposits (P < 0.001). There were no significant differences in clinical features between the groups. Two children with SMGN underwent a repeat biopsy 3 yr after the first biopsy, and both patients again showed SMGN. At the final observation (mean observation time 7.5 yr in SMGN and 12.4 yr in GMGN), all children of both groups had a good outcome. In conclusion, these findings as a whole suggest that SMGN may be another glomerular disease entity with child predominance that is distinctive from GMGN.
    Jul. 2006, Clinical journal of the American Society of Nephrology : CJASN, 1(4) (4), 723 - 729, English, International magazine
    [Refereed]
    Scientific journal

  • Mina Obana, Koichi Nakanishi, Mayumi Sako, Nahoko Yata, Kandai Nozu, Ryojiro Tanaka, Kazumoto Iijima, Norishige Yoshikawa
    Generally, idiopathic membranous glomerulonephritis (MGN) is a global glomerular disease that affects the whole of the glomerulus. However, idiopathic segmental MGN (SMGN) that shows IgG deposits in a portion of the glomerulus is encountered often. For clarification of whether SMGN is the same entity as idiopathic global MGN (GMGN), the two diseases were compared. From 1978 to 2004,38 children (11 with SMGN and 27 with GMGN) received a diagnosis of idiopathic MGN. Immunofluorescence microscopy showed segmental granular IgG staining along the capillary loops in SMGN, whereas GMGN showed global staining. On light microscopy, SMGN showed segmental thickening of the glomerular basement membrane, with spike formation, whereas GMGN showed global lesions. The frequency of C1q deposits in SMGN was significantly higher than that in GMGN (91 versus 41%; P < 0.01). On electron microscopy, mesangial electron-dense deposits were detected in 10 (91%) cases of SMGN and also were found in the subepithelial and intramembranous area, whereas only six (22%) cases of GMGN had mesangial electron-dense deposits (P < 0.001). There were no significant differences in clinical features between the groups. Two children with SMGN underwent a repeat biopsy 3 yr after the first biopsy, and both patients again showed SMGN. At the final observation (mean observation time 7.5 yr in SMGN and 12.4 yr in GMGN), all children of both groups had a good outcome. In conclusion, these findings as a whole suggest that SMGN may be another glomerular disease entity with child predominance that is distinctive from GMGN.
    AMERICAN SOCIETY NEPHROLOGY, Jul. 2006, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 1(4) (4), 723 - 729, English
    [Refereed]
    Scientific journal

  • M Okada, R Fujimaru, N Morimoto, K Satomura, Y Kaku, K Tsuzuki, K Nozu, T Okuyama, K Iijima
    We isolated genomic DNA from 15 patients with branchio-oto-renal (BOR) syndrome or BOR-related conditions. Seven patients had BOR syndrome (two familial and five sporadic), and eight had deafness and renal malformations without branchial fistula (BOR-related conditions). We analyzed all exons and exon-intron boundaries of EYA1 and SIX1 using the polymerase chain reaction (PCR) direct sequencing, and characterized their mutations. In some patients, analysis of mRNA by reverse transcription (RT)-PCR was performed to examine whether the mutation affects the mRNA splicing. We identified five novel disease-causing heterozygous EYA1 mutations in five patients with BOR syndrome (two familial and three sporadic, 5/7=71%), but EYA1 and SIX1 mutations were not detected in the other two patients with BOR syndrome or any of the patients with BOR-related conditions. The detected EYA1 mutations were two nonsense mutations, two splicing acceptor-site mutations, and a point mutation (G > T) of the first base of exon 10. Analysis of mRNA by RT-PCR direct sequencing revealed that the latter point mutation led to the skipping of exon 10. In conclusion, (1) EYA1 mutations are a major cause of BOR syndrome in Japanese, (2) EYA1 and SIX1 mutations were not a major cause of BOR-related conditions, (3) we demonstrated for the first time that the point mutation (G > T) of the first base of the exon in EYA1 gene induced exon skipping.
    SPRINGER, Apr. 2006, PEDIATRIC NEPHROLOGY, 21(4) (4), 475 - 481, English
    [Refereed]
    Scientific journal

  • 全国調査における典型的HUSの重症化因子の検討
    神岡 一郎, 野津 寛大, 貝藤 裕史, 藤田 晃生, 吉矢 邦彦, 里村 憲一, 田中 亮二郎, 飯島 一誠, 中西 浩一, 吉川 徳茂, 松尾 雅文
    (一社)日本腎臓学会, Apr. 2006, 日本腎臓学会誌, 48(3) (3), 201 - 201, Japanese

  • 小児IgA腎症におけるTransforming Growth Factor(TGF)-β1遺伝子多型(C-509T,T869C)の関与
    尾鼻 美奈, 中西 浩一, 佐古 まゆみ, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2006, 日本腎臓学会誌, 48(3) (3), 236 - 236, Japanese

  • K Nozu, K Iijima, Kamioka, I, T Fujita, K Yoshiya, R Tanaka, K Nakanishi, N Yoshikawa, M Matsuo
    Background: In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose-dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE. Methods: The authors administered oral MZR at 300mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment. Results: Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 mu g/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months. Conclusion: MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.
    BLACKWELL PUBLISHING, Apr. 2006, PEDIATRICS INTERNATIONAL, 48(2) (2), 152 - 157, English
    [Refereed]
    Scientific journal

  • Alport症候群に対する抗アルドステロン薬の効果についての検討
    貝藤裕史, NOZU, kandai, 藤田晃生, 神岡一郎, 濱平陽史, 中西浩一, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (公社)日本小児科学会, Feb. 2006, 日本小児科学会雑誌, 110巻, 2号, pp.233-233(2) (2), 233 - 233, Japanese
    International conference proceedings

  • 竹田 雅, 兵頭 洋二, 石田 敏郎, 原 勲, 濱見 学, 松本 修, 野津 寛大, 吉川 徳茂, 藤澤 正人
    一般社団法人 日本泌尿器科学会, 2006, 日本泌尿器科学会雑誌, 97(2) (2), 413 - 413, Japanese

  • Toshiyuki Sakaeda, Kazumoto Iijima, Kandai Nozu, Tsutomu Nakamura, Yuka Moriya, Mika Nishikawa, Atsushi Wada, Noboru Okamura, Masafumi Matsuo, Katsuhiko Okumura
    The monitoring of the blood concentration at 2 h (C-2) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the area under the blood concentration-time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a greater correlation for C-2 (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC(0-4) was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22-31% lower in the patients with TT3435. Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0-4). A strong effect was also observed for the serum total cholesterol level.
    SPRINGER TOKYO, 2006, JOURNAL OF HUMAN GENETICS, 51(11) (11), 969 - 976, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 膜性腎症を伴ったslowly progressive IDDMの男性の1例
    神岡 一郎, 西山 敦史, 藤田 晃生, 石橋 和人, 野津 寛大, 竹島 泰弘, 松尾 雅文, 八木 麻理子, 吉川 徳茂
    (公社)日本小児科学会, Dec. 2005, 日本小児科学会雑誌, 109(12) (12), 1474 - 1474, Japanese

  • 尿中落下細胞を用いた解析で遺伝子変異を証明できたGitelman症候群の1例
    貝藤裕史, NOZU, kandai, 藤田晃生, 神岡一郎, 付学軍, MATSUO, Masafumi, 住永亮, 石田明人
    Dec. 2005, 日本小児科学会雑誌, 109巻, 12号, pp.1478-1478, Japanese
    International conference proceedings

  • マイコプラズマ感染を契機に発症したEVANS症候群の1例
    岡本龍, 藤田晃生, 神岡一郎, NOZU, kandai, HAYAKAWA, Akira, KAWASAKI,Keiichiro, TAKESHIMA, Yasuhiro, MATSUO, Masafumi
    (公社)日本小児科学会, Dec. 2005, 日本小児科学会雑誌, 109巻, 12号, pp.1472-1473(12) (12), 1472 - 1473, Japanese
    International conference proceedings

  • 藤田晃生, NOZU, kandai, 貝藤裕史, 神岡一郎, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    小児期に発症し，各種免疫抑制剤の投与でも完全寛解に至らず，成人期にキャリーオーバーした難治性ネフローゼ症候群に対し，ミコフェノール酸モフェチルを投与し良好な経過を得た2例について報告する。２例とも幼少期にネフローゼ症候群を発症し，頻回に再発を繰り返したためシクロスポリン，シクロフォスファミド，ミゾリビンなどの各種免疫抑制剤を投与されていた。いずれも成人期にキャリーオーバーし，シクロスポリンの腎毒性，シクロフォスファミドの投与量限界などから既存の免疫抑制剤による寛解は困難と判断し，ミコフェノール酸モフェチルの投与を開始した。症例１は投与開始直後と12カ月後にそれぞれ再発を認めたものの尿蛋白は速やかに消失し，症例２は投与開始後10カ月間再発を認めておらず，いずれも良好な臨床経過である。ミコフェノール酸モフェチルは副作用も少なく，難治性ネフローゼ症候群に対する効果が期待されており，今後長期に経過を観察し効果を見極める必要があると思われた。
    The Japanese Society for Pediatric Nephrology, Nov. 2005, 日本小児腎臓病学会雑誌, 18巻, 2号, pp.131-135(2) (2), 131 - 135, Japanese
    [Refereed]
    Scientific journal

  • K Nozu, K Iijima, M Fujisawa, A Nakagawa, N Yoshikawa, M Matsuo
    A 12-year-old Japanese boy who underwent kidney transplantation with a kidney from his mother developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS) and electron microscopic examination of the renal biopsy showed foot process fusion, we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney. Four months after the transplantation, posttransplant lymphoproliferative disorder (PTLD) developed, which was pathologically diagnosed as diffuse large B cell lymphoma. Treatment consisting of a reduction in immunosuppression resulted in improvement in PTLD a month after the start of treatment. However, relapse occurred 2 months after the first onset of PTLD, which we treated with rituximab (CD-20 monoclonal antibody 375 mg/m(2)) once weekly for a total of four doses. The PTLD resolved immediately after the rituximab treatment was started, and, interestingly, urinary protein levels also improved at the same time. Three years later, the boy shows no signs of PTLD, and no proteinuria has been detected. These findings suggest that rituximab may be an effective treatment for recurrence of nephrotic syndrome after transplantation and that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation.
    SPRINGER, Nov. 2005, PEDIATRIC NEPHROLOGY, 20(11) (11), 1660 - 1663, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 竹田 雅, 兵頭 洋二, 石田 敏郎, 野津 寛大, 吉川 徳茂, 藤澤 正人
    (一社)日本移植学会, Oct. 2005, 移植, 40(総会臨時) (総会臨時), 209 - 209, Japanese

  • 腎機能が保たれている時期に腹膜透析を導入した難治性ネフローゼ症候群の1例
    NOZU, kandai, 藤田晃生, 神岡一郎, MATSUO, Masafumi, 吉矢邦彦, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川徳茂
    Aug. 2005, 日本小児腎不全学会雑誌, 25巻, pp.138-140, 138 - 140, Japanese
    [Refereed]
    Scientific journal

  • 当院における溶血性尿毒症症候群の臨床的検討
    藤田晃生, 神岡一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢邦彦, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (一社)日本腎臓学会, May 2005, 日本腎臓学会誌, 47巻, 3号, pp.353-353(3) (3), 353 - 353, Japanese
    International conference proceedings

  • 維持血液透析を施行している小児末期腎不全の1症例
    横山朋大, 竹田陽子, 土橋大輔, 藤井秀毅, 土岐岳志, ABE, Takaya, UMEDU, Michio, NOZU, kandai, MATSUO, Masafumi, FUKAGAWA, Masafumi
    (一社)日本透析医学会, May 2005, 日本透析医学会雑誌, 38巻, Suppl.1, pp.1227-1227(Suppl.1) (Suppl.1), 1227 - 1227, Japanese
    International conference proceedings

  • 膜性増殖性糸球体腎炎(MPGN)24例の長期予後に関する検討
    藤田晃生, 神岡一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢邦彦, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (一社)日本小児腎臓病学会, Apr. 2005, 日本小児腎臓病学会雑誌, 18巻, 1Suppl., pp.180-180(1Suppl.) (1Suppl.), 180 - 180, Japanese
    International conference proceedings

  • 全国調査における典型的溶血性尿毒症症候群の治療の検討
    神岡一郎, NOZU, kandai, 藤田晃生, 吉矢邦彦, 里村憲一, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (一社)日本小児腎臓病学会, Apr. 2005, 日本小児腎臓病学会雑誌, 18巻, 1Suppl., pp.184-184(1Suppl.) (1Suppl.), 184 - 184, Japanese
    International conference proceedings

  • Gene Scanを用いることで遺伝子異常を発見できた3型バーター症候群の1例
    NOZU, kandai, 付学軍, NISHIO, Hisahide, 神岡一郎, 藤田晃生, 吉矢邦彦, 郷司克己, IIJIMA,Kazumoto
    Apr. 2005, 日本小児腎臓病学会雑誌, 18巻, 1Suppl., pp.144-144, Japanese
    International conference proceedings

  • 小児腎疾患患者におけるCsA体内動態に及ぼす併用薬・腎機能の影響
    西川美香, 守屋友加, 中村任, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    (公社)日本薬剤学会, Mar. 2005, 薬剤学, 65巻, Suppl., pp. 122-122(Suppl.) (Suppl.), 122 - 122, Japanese
    International conference proceedings

  • 当院における溶血性尿毒症症候群(HUS)の臨床的検討
    藤田晃生, 神岡一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢邦彦, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (公社)日本小児科学会, Feb. 2005, 日本小児科学会雑誌, 109巻, 2号, pp. 239-239(2) (2), 239 - 239, Japanese
    International conference proceedings

  • 全国調査における典型的溶血性尿毒症候群の重症化因子の検討
    神岡一郎, NOZU, kandai, 藤田晃生, 吉矢邦彦, 里村憲一, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (公社)日本小児科学会, Feb. 2005, 日本小児科学会雑誌, 109巻, 2号, pp. 149-149(2) (2), 149 - 149, Japanese
    International conference proceedings

  • 腹膜透析を導入した頻回再発型ネフローゼ症候群の1例
    藤田晃生, 神岡一郎, NOZU, kandai, MATSUO, Masafumi
    Dec. 2004, 日本小児科学会雑誌, 108巻, 12号, pp. 1515-1515, Japanese
    International conference proceedings

  • 治療抵抗性で腎不全へと至り,移植後再発のため再び腎不全へと至った,微小変化型ネフローゼの1例
    大沼健一, 藤田晃生, 神岡一郎, NOZU, kandai, MATSUO, Masafumi, 亀田愛樹, TANAKA,Ryojiro
    Dec. 2004, 日本小児科学会雑誌, 108巻, 12号, pp. 1513-1513, Japanese
    International conference proceedings

  • タクロリムスが有効であった難治性ネフローゼ症候群の2例
    神岡一郎, 藤田晃生, NOZU, kandai, MATSUO, Masafumi, TANAKA,Ryojiro, 河田知子, 上原愼一郎, 吉川徳茂
    (公社)日本小児科学会, Dec. 2004, 日本小児科学会雑誌, 108巻, 12号, pp. 1522-1522(12) (12), 1522 - 1522, Japanese
    International conference proceedings

  • 神岡一郎, NOZU, kandai, 藤田晃生, TANAKA,Ryojiro, 吉矢邦彦, 北川康作, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    MPO-ANCA (myeloperoxidase anti-neutrophil cytoplasmic autoantibody) が陽性のANCA関連血管炎症候群の2症例について報告する。
    症例1は7歳の女児。間質性肺炎と軽度の腎機能障害で発症した。ステロイドパルス療法の後, 多剤併用療法を行ったが, 徐々に腎機能は悪化し発症4年後に腹膜透析導入となった。現在は原疾患の再燃もなく腹膜透析継続中である。
    症例2は6歳の女児。肺出血と高度の腎機能障害で発症し, 入院当日より腹膜透析を導入した。またステロイドパルス療法を行い肺出血はいったん改善したがすぐに再出血し人工呼吸管理を要した。2度目のステロイドパルス療法は効果がなく, 血漿交換療法を行ったところ劇的に呼吸状態は改善し一命を取りとめた。しかし腎機能は改善せず現在も腹膜透析を継続している。
    2症例はどちらも末期腎不全へと移行し腎予後が不良であった。またステロイドパルス療法が無効例の呼吸器症状に対しては血漿交換療法も考慮すべきと考えられた。
    The Japanese Society for Pediatric Nephrology, Nov. 2004, 日本小児腎臓病学会雑誌, 17巻, 2号, pp. 95-101(2) (2), 95 - 101, Japanese
    [Refereed]
    Scientific journal

  • XJ Fu, K Iijima, K Nozu, K Hamahira, R Tanaka, T Oda, N Yoshikawa, M Matsuo
    The role of proinflammatory cytokines in a rat model of toxin-induced hemolytic uremic syndrome (HUS) was studied. Male Sprague-Dawley rats underwent continuous saline infusion (6 ml/h) via a tail vein and received a bolus injection of saline (control), lipopolysaccharide (LPS, 10 mug/100 g body weight), ricin (6.7 mug/100 g body weight), or ricin with LPS (ricin+LPS). They were then observed for 8 h. Blood samples and kidney tissues were obtained at the end of the experiment. The effects of FR 167653, a potent inhibitor of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production, were also examined in ricin+LPS-treated rats. Only ricin+LPS-treated rats developed significant thrombocytopenia, hemolysis, and oliguric acute renal failure with extensive glomerular thrombotic microangiopathy, which was characterized by glomerular microthrombi and apoptosis of glomerular endothelial cells. Thrombotic microangiopathy was not detected in other organs, including the brain, liver, spleen, pancreas, lung, colon, and intestine. Significantly elevated levels of serum IL-1beta and TNF-alpha were detected only in ricin+LPS-treated rats. Treatment of ricin+LPS-treated rats with FR 167653 significantly reduced the serum levels of IL-1beta and TNF-alpha, accompanied by improvement of the oliguric renal failure and glomerular thrombotic microangiopathy. These findings indicate that the increased serum levels of IL-1beta and TNF-alpha, which probably result in the apoptosis of glomerular endothelial cells, play a pivotal role in the development of this rat model of toxin-induced HUS. The findings also suggest that inhibition of these proinflammatory cytokines may prevent the development of HUS.
    SPRINGER, Aug. 2004, PEDIATRIC NEPHROLOGY, 19(8) (8), 844 - 852, English
    [Refereed]
    Scientific journal

  • 頻回の嘔吐に伴い一過性の急性腎不全を繰り返した1例
    Nozu Kandai
    Aug. 2004, 日本小児腎不全学会雑誌, 24巻, , pp. 98-100, Japanese
    [Refereed]
    Scientific journal

  • 小児患者におけるCyclosporineの体内動態とMDR1遺伝子多型の関連性
    西川美香, 山下智美, 守屋友加, 中村任, YAGI, Mariko, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    (一社)日本臨床薬理学会, Aug. 2004, 臨床薬理, 35巻, Suppl., pp. S151-S151(Suppl.) (Suppl.), S151 - S151, Japanese
    International conference proceedings

  • Blood accessの確保に難渋し,維持血液透析を余儀なくされた2歳女児例
    Nozu Kandai
    Aug. 2004, 日本小児腎不全学会雑誌, 24巻, , pp. 149-152, 149 - 152, Japanese
    [Refereed]
    Scientific journal

  • Rituximabの投与が,FSGSの移植後再発に対し有効であったと考えられた1例 FSGSとBリンパ球活性化の関与に関する考察
    野津 寛大, 神岡 一郎, 藤田 晃生, 吉矢 邦彦, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2004, 日本小児腎臓病学会雑誌, 17(1Suppl.) (1Suppl.), 102 - 102, Japanese

  • 北村 明子, 香美 祥二, 塚口 裕康, 荒木 淳吾, 村松 正明, 野津 寛大, 星井 桜子, 金田 尚, 池田 昌弘, 服部 元史, 本田 雅敬, 吉川 徳茂, 黒田 泰弘, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2004, 日本小児腎臓病学会雑誌, 17(1Suppl.) (1Suppl.), 131 - 131, Japanese

  • 巣状膜性糸球体腎炎(FMGN) びまん性膜性糸球体腎炎(DMGN)との比較検討
    尾鼻 美奈, 中西 浩一, 佐古 まゆみ, 矢田 菜穂子, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2004, 日本小児腎臓病学会雑誌, 17(1Suppl.) (1Suppl.), 190 - 190, Japanese

  • 当院で経験したANCA関連血管炎症候群の2例の検討
    神岡一郎, 藤田晃生, NOZU, kandai, MATSUO, Masafumi, 浜平陽史, TANAKA,Ryojiro, 北川康作, IIJIMA,Kazumoto, 吉川徳茂
    (一社)日本小児腎臓病学会, Jun. 2004, 日本小児腎臓病学会雑誌, 17巻, 1Suppl., pp. 158-158(1Suppl.) (1Suppl.), 158 - 158, Japanese
    International conference proceedings

  • Bartter症候群8例における遺伝子解析
    付学軍, NOZU, kandai, 神岡一郎, 藤田晃生, MATSUO, Masafumi, 吉矢邦彦, 宮下律子, 島雅昭, 中島敏博, 中西浩一, 吉川徳茂, IIJIMA,Kazumoto
    (一社)日本小児腎臓病学会, Jun. 2004, 日本小児腎臓病学会雑誌, 17巻, 1Suppl., pp. 141-141(1Suppl.) (1Suppl.), 141 - 141, Japanese
    International conference proceedings

  • 日本人家族性巣状分節性糸球体硬化症におけるαアクチニン4遺伝子とポドシン遺伝子変異の検索
    佐古 まゆみ, 中西 浩一, 矢田 菜穂子, 尾鼻 美奈, 野津 寛大, 田中 亮二郎, 飯島 一誠, 池田 昌弘, 本田 雅敬, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2004, 日本腎臓学会誌, 46(3) (3), 220 - 220, Japanese

  • 当院における典型的MPGN及びAtypical MPGNの臨床的検討
    藤田晃生, 神岡一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢邦彦, IIJIMA,Kazumoto, 吉川徳茂, MATSUO, Masafumi
    (一社)日本腎臓学会, Apr. 2004, 日本腎臓学会誌, 46巻, 3号, pp. 234-234(3) (3), 234 - 234, Japanese
    International conference proceedings

  • K Nakanishi, M Sako, N Yata, N Aoyagi, K Nozu, R Tanaka, K Iijima, N Yoshikawa
    We have previously reported that the TT genotype of the angiotensinogen gene and the ID/DD genotype of the angiotensin-converting enzyme gene are associated with increased severity of proteinuria in IgA nephropathy in Japanese children. Recently it was reported that polymorphism at -20 from adenine to cytosine in the angiotensinogen gene, increasing the level of this transcript, was associated with the progression of renal dysfunction in adult IgA nephropathy. We therefore investigated whether this polymorphism is involved in IgA nephropathy in Japanese children. We identified this polymorphism in 105 children with IgA nephropathy and 119 healthy adults using polymerase chain reaction/restriction fragment length polymorphism analysis. At the time of biopsy, all patients had normal blood pressure and renal function. There were no differences in the genotypes and allele frequencies of this polymorphism between patients with IgA nephropathy and controls. The number of patients with the AC/CC genotype showing heavy proteinuria (greater than or equal to1.0 g/day per m(2) body surface area) at biopsy was significantly higher than that with the AA genotype (P=0.039, chi-squared test). The AC/CC genotype of this polymorphism may be associated with an increased severity of proteinuria, suggesting that this polymorphism may play a significant role in the progression of IgA nephropathy in Japanese children.
    SPRINGER-VERLAG, Feb. 2004, PEDIATRIC NEPHROLOGY, 19(2) (2), 144 - 147, English
    [Refereed]
    Scientific journal

  • 非典型的膜性増殖性糸球体腎炎(Atypical MPGN)の臨床的検討
    藤田晃生, 神岡一郎, NOZU, kandai, 吉川徳茂, MATSUO, Masafumi
    (公社)日本小児科学会, Feb. 2004, 日本小児科学会雑誌, 108巻, 2号, pp. 323-323(2) (2), 323 - 323, Japanese
    International conference proceedings

  • キャンピロバクター腸炎後に溶血性尿毒症症候群を発症し末期腎不全へと至った7歳女児例
    神岡一郎, 藤田晃生, NOZU, kandai, MATSUO, Masafumi, 石田敏郎, TAKEDA, Masashi, TANAKA,Ryojiro, 吉矢邦彦, IIJIMA,Kazumoto, 吉川徳茂
    2004, 日本小児腎不全学会雑誌, 24巻, pp. 142-145, 142 - 145, Japanese
    Scientific journal

  • 巣状分節性糸球体硬化症(FSGS)は微小変化に改善しうる
    田中 亮二郎, 神岡 一郎, 野津 寛大, 中村 肇, 松尾 雅文, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2003, 日本小児腎臓病学会雑誌, 16(1Suppl.) (1Suppl.), 174 - 174, Japanese

  • 急性腎不全を合併した小児ネフローゼ症候群12例の臨床病理学的検討
    矢田 菜穂子, 中西 浩一, 佐古 まゆみ, 田中 亮二郎, 野津 寛大, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2003, 日本小児腎臓病学会雑誌, 16(1Suppl.) (1Suppl.), 177 - 177, Japanese

  • 非典型的な経過をとり腎生検を施行した溶血性尿毒症症候群についての検討
    神岡 一郎, 野津 寛大, 田中 亮二郎, 中村 肇, 松尾 雅文, 吉矢 邦彦, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2003, 日本小児腎臓病学会雑誌, 16(1Suppl.) (1Suppl.), 186 - 186, Japanese

  • 小児におけるネオーラル薬物動態に関する研究
    NOZU, kandai, 神岡一朗, TANAKA,Ryojiro, MATSUO, Masafumi, 和田敦, 喜多知子, SAKAEDA, Toshiyuki, OKUMURA, Katsuhiko, 本田雅敬, 池田昌弘, IIJIMA,Kazumoto
    Jun. 2003, 日本小児腎臓病学会雑誌, 16巻, Suppl.1, pp. 132-132, Japanese
    International conference proceedings

  • 小児におけるネオーラル薬物動態に関する研究
    NOZU, kandai, 神岡一郎, SAKAEDA, Toshiyuki, 喜多知子, 和田敦, OKUMURA, Katsuhiko, TANAKA,Ryojiro, NAKAMURA,Hajime, MATSUO, Masafumi, 本田雅敬, 池田昌弘, IIJIMA,Kazumoto
    (一社)日本腎臓学会, Apr. 2003, 日本腎臓学会誌, 45巻, 3号, pp. 251-251(3) (3), 251 - 251, Japanese
    International conference proceedings

  • Katsuyasu Saigo, M. Jiang, C. Tanaka, K. Fujimoto, A. Kobayashi, K. Nozu, K. Iijima, R. Ryo, T. Sugimoto, S. Imoto, S. Kumagai
    We previously reported an automatic method for quantitative analysis of schistocytes or fragmented red cells using an automatic hematology analyzer, XE-2100. In the study reported here, we evaluated the accuracy of this detection method in patients with thrombotic microangiopathy (TMA). A follow-up study was performed on 14 patients with two types of TMA, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Schistocyte percent was evaluated both with an automatic counter and by means of microscopic observation. Total activity and isoenzyme pattern of lactate dehydrogenase (LD) were also determined. In these patients, schistocyte percent determined by automatic counting correlated highly with that determined by manual counting under microscopic observation (r = 0.852, P < 0.0001). Schistocyte percent was shown to correlate significantly with isoenzyme fractions 1 and 2 of LD (r = 0.732, P < 0.02), reflecting hemolysis. Nine of 11 patients tested had high concentrations of LD isoenzyme five without distinct liver damage, and schistocyte percent did not relate to fraction 5 of LD. Automatic detection of schistocyte percent using a hematology analyzer was useful for an accurate diagnosis and follow-up of thrombotic microangiopathy. The origin of LD fraction 5 remains to be determined.
    Dec. 2002, Clinical and Laboratory Haematology, 24(6) (6), 347 - 351, English
    [Refereed]
    Scientific journal

  • 小児期ネオーラル内服患者におけるシクロスポリン血中濃度モニタリングの検討
    野津 寛大, 田中 亮二郎, 飯島 一誠, 中村 肇, 喜多 知子, 栄田 敏之, 奥村 勝彦
    (一社)日本小児腎臓病学会, Jun. 2002, 日本小児腎臓病学会雑誌, 15(1Suppl.) (1Suppl.), 142 - 142, Japanese

  • K Iijima, K Hamahira, R Tanaka, A Kobayashi, K Nozu, H Nakamura, N Yoshikawa
    Background. Cyclosporine (CsA) is effective for the treatment of children with steroid-dependent and -resistant nephrotic syndrome (NS), but it can result in chronic CsA nephrotoxicity including CsA-induccd tubulointerstitial lesions. The factors responsible for the development of CsA-induced tubulointerstitial lesions arc unknown. Methods. To identify the risk factors for the development of CsA-induced tubulointerstitial lesions in children with minimal change NS who had been treated with long-term moderate dose CsA, we compared several clinical and laboratory factors of 37 patients with and without CsA-induced tubulointerstitial lesions by the Mann-Whitney U test, Fisher's exact test, and stepwise logistic-regression analysis. Results. Thirteen patients had CsA-induced tubulointerstitial lesions and 24 patients had none. Among clinical and laboratory factors, the duration of CsA treatment (P = 0.003) and the duration of heavy proteinuria during CsA treatment (P = 0.024) were related to the development of CsA-induced tubulointerstitial lesions as determined by the univariate analyses. Indeed, CsA-induced tubulointerstitial lesions were found in 2 of 18 (11%) patients who had been treated with CsA for less than 24 months, but in 11 of 19 patients (58%) who had been treated for more than 24 months (P = 0.005). They were also found in 4 of 23 patients (17%) who had heavy proteinuria for less than 30 days during CsA treatment, but in 9 of 14 patients (64%) who had heavy proteinuria for more than 30 days (P = 0.006), Stepwise logistic-regression analysis revealed that the duration of CsA treatment for more than 24 months (X-2 = 6.203, P = 0.013) and the duration of heavy proteinuria during CsA treatment for more than 30 days (X-2 = 5,871, P = 0.015) were independent risk factors for the development of CsA-induccd tubulointerstitial lesions. Conclusions. Duration of the CsA treatment and the duration of heavy proteinuria during CsA treatment were independent significant risk factors for the development of CsA- induced tubulointerstitial lesions in children with MCNS who had been treated with long-term moderate-dose CsA.
    BLACKWELL PUBLISHING INC, May 2002, KIDNEY INTERNATIONAL, 61(5) (5), 1801 - 1805, English
    [Refereed]
    Scientific journal

  • ACE阻害剤及びアンギオテンシンI受容体拮抗薬を投与したアルポート症候群の5例
    小林 明子, 浜平 陽史, 飯島 一誠, 中村 肇, 吉川 徳茂, 野津 寛大, 桜井 隆, 児玉 荘一
    日本小児腎不全学会, Aug. 2001, 日本小児腎不全学会雑誌, 21, 140 - 140, Japanese

  • ACE阻害剤及びアンギオテンシンI受容体拮抗薬を投与したアルポート症候群の5例
    小林 明子, 浜平 陽史, 飯島 一誠, 中村 肇, 吉川 徳茂, 野津 寛大, 桜井 隆, 児玉 荘一
    (株)メディカルレビュー社, Sep. 2000, Pharma Medica, 18(9) (9), 187 - 187, Japanese

  • Alport Syndrome
    Kandai Nozu, Tomohiko Yamamura, Tomoko Horinouchi
    CLINICAL CHARACTERISTICS: Alport syndrome is characterized by kidney manifestations, sensorineural hearing loss (SNHL), and ocular manifestations. In the absence of treatment, kidney disease progresses from microhematuria to proteinuria, progressive kidney insufficiency, and end-stage kidney disease (ESKD) in most males with X-linked Alport syndrome (XLAS), and in most males and females with autosomal recessive Alport syndrome (ARAS). Progressive SNHL is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In females with XLAS and individuals with autosomal dominant Alport syndrome (ADAS), ESKD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare. DIAGNOSIS/TESTING: The molecular diagnosis of Alport syndrome is established in a proband with suggestive findings and a pathogenic variant(s) in COL4A3, COL4A4, or COL4A5 identified by molecular genetic testing. Kidney biopsy, skin biopsy (in some individuals with XLAS), or clinical diagnostic criteria may be used to establish the diagnosis in those without access to genetic testing or those with uninformative results. MANAGEMENT: Treatment of manifestations: Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to delay onset of ESKD; standard treatment of hypertension; kidney transplantation for ESKD. Potential living related donors must be evaluated carefully to avoid nephrectomy in an affected individual. Hearing aids as needed for SNHL; cataract removal as needed; in those with deletions of COL4A5 extending into intron 2 of COL4A6, surgical intervention for symptomatic leiomyomas as needed. Surveillance: Evaluation by a nephrologist including urinalysis, assessment of kidney function, and blood pressure every six to 12 months; monthly monitoring of at-risk transplant recipients for development of anti-glomerular basement membrane antibody-mediated glomerulonephritis for the first year post transplant; audiologic evaluation every one to two years beginning at age six to seven years; ophthalmology evaluation for ocular abnormalities every one to two years beginning in adolescence in males with a COL4A5 truncating pathogenic variant and in persons with ARAS. Agents/circumstances to avoid: Drink adequate fluids as dehydration may accelerate the progression of nephropathy. Protection of corneas from minor trauma in those with recurrent corneal erosions. Minimize exposure to loud noise. Evaluation of relatives at risk: Evaluate at-risk family members in order to identify as early as possible those who would benefit from initiation of treatment either by molecular genetic testing if the pathogenic variant(s) in the family are known or urinalysis and blood pressure if the pathogenic variant(s) in the family are not known. GENETIC COUNSELING: COL4A5-related Alport syndrome is inherited in an X-linked manner (XLAS). COL4A3- and COL4A4-related Alport syndrome are inherited in an autosomal dominant (ADAS) or autosomal recessive (ARAS) manner. Digenic Alport syndrome is caused by pathogenic variants in more than one Alport syndrome-related gene: typically pathogenic variants in both COL4A3 and COL4A4 (in cis or in trans) or, more rarely, a pathogenic variant in COL4A5 in addition to a pathogenic variant in COL4A3 or COL4A4. XLAS: The risk to sibs of a male proband depends on the genetic status of the mother: if the mother of the proband has a COL4A5 pathogenic variant, the chance of transmitting it in each pregnancy is 50%. The risk to the sibs of a female proband depends on the genetic status of the parents: if the mother of the proband has a COL4A5 pathogenic variant, the chance of transmitting it in each pregnancy is 50%; if the father of the proband has a COL4A5 pathogenic variant, he will transmit it to all of his daughters and none of his sons. Males and females who inherit the pathogenic variant will be affected. ARAS: If both parents are known to be heterozygous for a COL4A3 or COL4A4 pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants (and having ARAS), a 50% chance of being heterozygous (and at risk for ADAS), and a 25% chance of inheriting neither of the familial pathogenic variants. ADAS: If a parent of the proband is affected and/or is known to have the COL4A3 or COL4A4 pathogenic variant identified in the proband, the risk to sibs of inheriting the pathogenic variant is 50%. The severity of clinical manifestations may vary greatly among heterozygous family members; some heterozygotes may be asymptomatic and some may develop ESKD. Digenic Alport syndrome: The risk to sibs depends on the involved genes, the location of the pathogenic variants (i.e., in cis or in trans) in families segregating pathogenic variants in COL4A3 and COL4A4, and the sex of the proband (in families segregating pathogenic variants in COL4A5 and COL4A3 or COL4A4). Once the Alport syndrome-related pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
    University of Washington, Seattle, 1993, English

■ MISC
  • 副腎皮質腫瘍を合併したBeckwith-Wiedemann症候群の一例
    杉村竜太郎, 西村明紘, 藤川朋子, 井上翔太郎, 田村彰広, 山本暢之, 野津寛大, 尾藤裕子, 大片祐一, 亀岡泰幸
    2024, 近畿小児科学会プログラム・抄録集, 37th

  • 劇症型経過をたどり外科的治療を要した小児潰瘍性大腸炎の2例
    大塚優治, 近藤淳, 猪野木雄太, 市川裕太, 田中悠, 北角英晶, 堀之内智子, 大片祐一, 尾藤祐子, 野津寛大
    2024, 近畿小児科学会プログラム・抄録集, 37th

  • Alport症候群原因遺伝子COL4A5の各種exon欠損がIV型コラーゲン三量体分泌に与える影響
    小山結実, SUICO Mary Ann, 加世田将大, 桑水流淳, 三宮裕也, 堀園潤, 津波古遥希, 尾脇あいみ, 佐藤諒一, 白神正博, 首藤剛, 山村智彦, 野津寛大, 甲斐広文
    2023, 日本小児腎臓病学会雑誌(Web), 36

  • Frontometaphyseal dysplasia type1の遺伝学的診断と遺伝カウンセリング
    洪本加奈, 森貞直哉, 森貞直哉, 森貞直哉, 野津寛大, 大津雅秀, 小林大介
    2023, 日本整形外科学会雑誌, 97(9) (9)

  • 当院で経験した希少先天性グリコシル化異常症(CDG)の2女児例
    森貞直哉, 森貞直哉, 洪本加奈, 藤代瞳, 親里嘉展, 野津寛大, 小崎健次郎, 角谷真知子, 和田芳直, 岡本伸彦, 岡本伸彦
    2023, 日本先天代謝異常学会雑誌, 39

  • こどもたちへの遺伝カウンセリング後に診断を確定したOptic atrophy plus症候群の親子例
    森貞直哉, 森貞直哉, 森貞直哉, 洪本加奈, 坂田亮介, 小川禎治, 横田聡, 前川嵩太, 苅田典生, 野津寛大
    2023, 日本小児遺伝学会学術集会プログラム・抄録集, 46th

  • 電解質異常から発見する小児遺伝性腎疾患 バーター症候群・ギッテルマン症候群
    野津 寛大
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 215 - 215, Japanese

  • 生後早期のアルドステロン測定により診断にいたった早産児のI型偽性低アルドステロン症の1例
    角谷哲基, 牟禮岳男, 榎本真由子, 藤坂方葉, 水野洋介, 下村真由美, 西野昌光, 野津寛大, 飯島一誠, 吉井勝彦
    2022, 小児内科, 54(1) (1)

  • Genetic autopsyで17q12欠失症候群と診断したPotter sequenceの1男児例
    洪本加奈, 森貞直哉, 森貞直哉, 森貞直哉, 平久進也, 大西徳子, 大西徳子, 船越徹, 野津寛大, 飯島一誠, 飯島一誠
    2022, 日本人類遺伝学会大会プログラム・抄録集, 67th (CD-ROM)

  • 周期的な不機嫌を呈したBosch-Boonstra-Schoaf optic atrophy syndromeの1例
    大西徳子, 大西徳子, 洪本加奈, 森貞直哉, 森貞直哉, 森貞直哉, 佐伯啓介, 野津寛大
    2022, 日本人類遺伝学会大会プログラム・抄録集, 67th (CD-ROM)

  • Genetic counseling for a sibling and their families with Marfan syndrome and X-linked hyper IgM syndrome
    洪本加奈, 森貞直哉, 森貞直哉, 中村さやか, 齋藤敦郎, 城戸佐知子, 小林大介, 野村耕治, 野津寛大
    2022, 日本遺伝カウンセリング学会誌, 43(1) (1)

  • 【小児疾患診療のための病態生理2 改訂第6版】腎・泌尿器疾患 繊毛病
    榊原 菜々, 森貞 直哉, 野津 寛大
    (株)東京医学社, Dec. 2021, 小児内科, 53(増刊) (増刊), 484 - 490, Japanese

  • 野津 寛大, 堀之内 智子, 山村 智彦
    (株)診断と治療社, Nov. 2021, 小児科診療, 84(11) (11), 1436 - 1440, Japanese

  • 飯島 一誠, 堀之内 智子, 賈 暁媛, 野津 寛大, 徳永 勝士
    (株)東京医学社, Nov. 2021, 腎と透析, 91(5) (5), 837 - 843, Japanese

  • 堀之内 智子, 野津 寛大
    ＜文献概要＞Point ◎遺伝性腎疾患は多岐にわたるが,臨床診断が困難な場合,臨床情報と遺伝学的検査を併せて検討することで正確な診断につながることがある.◎特に,疾患特異的な治療が存在する常染色体優性多発性嚢胞腎(ADPKD)やFabry病およびレニン・アンジオテンシン系(RAS)阻害薬が有効であるAlport症候群などではできるだけ早期の正確な診断が重要である.◎近年,次世代シークエンサーの進歩により,網羅的にさまざまな遺伝学的検査を行うことが可能となっている.◎遺伝学的検査に際しては,各種ガイドラインや指針の趣旨をよく理解しておく必要がある.
    (株)医学書院, Sep. 2021, Medicina, 58(10) (10), 1651 - 1654, Japanese

  • 長野 智那, 野津 寛大
    (有)科学評論社, Sep. 2021, 腎臓内科, 14(3) (3), 329 - 335, Japanese

  • 【腎疾患治療薬update】(第1章)腎疾患患者への薬の使い方 小児難治性ネフローゼ症候群 リツキシマブ
    飯島 一誠, 堀之内 智子, 野津 寛大, 佐古 まゆみ
    (株)東京医学社, Aug. 2021, 腎と透析, 91(増刊) (増刊), 76 - 80, Japanese

  • 【腎疾患治療薬update】(第5章)期待される薬剤 アルポート症候群の治療 RAS系阻害薬、バルドキソロンメチル、核酸医薬
    野津 寛大, 山村 智彦, 堀之内 智子, 飯島 一誠
    (株)東京医学社, Aug. 2021, 腎と透析, 91(増刊) (増刊), 808 - 811, Japanese

  • 山村 智彦, 野津 寛大
    (株)東京医学社, Jul. 2021, 腎と透析, 91(1) (1), 89 - 93, Japanese

  • 遺伝性腎疾患研究最前線:国内で行われている最先端の研究に触れる OCRL異常によるLowe症候群およびDent disease-2の発症メカニズム
    榊原 菜々, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 392 - 392, Japanese

  • 遺伝性腎疾患研究最前線:国内で行われている最先端の研究に触れる アルポート症候群に対する治療法の開発
    野津 寛大
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 392 - 392, Japanese

  • 嚢胞性腎疾患:現在の課題を認識し未来におけるより良い診療を創造するためのシンポジウム 遺伝学的解析が嚢胞性腎疾患診療に与えてきたインパクトと課題
    森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Jun. 2021, 日本腎臓学会誌, 63(4) (4), 395 - 395, Japanese

  • 野津 寛大
    (株)文光堂, May 2021, Medical Practice, 38(5) (5), 727 - 733, Japanese

  • 森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 67 - 67, Japanese

  • 野津 寛大, 森貞 直哉, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2021, 日本小児腎臓病学会雑誌, 34(1Suppl.) (1Suppl.), 68 - 68, Japanese

  • 堀之内 智子, 野津 寛大, 飯島 一誠
    (株)診断と治療社, Apr. 2021, 小児科診療, 84(増刊) (増刊), 306 - 309, Japanese

  • 堀之内 智子, 野津 寛大
    ＜文献概要＞維持輸液療法は,かつては3号液(3分の1生食)を4-2-1ルールに基づく投与量で行うことが一般的であった.しかし,非浸透圧刺激性ADH分泌による医原性低Na血症発症の可能性を少しでも低下させるため,現在は等張液で開始のうえ,必要に応じて輸液内の電解質を調節することが推奨されている.一方で等張液を用いた維持輸液においては低K血症,高Na血症のリスクがある.一律にすべての患者において同じマニュアルで輸液製剤を決めるのではなく,インアウトバランスを中心に患者の状態を適切に判断し,輸液の組成および投与量を決定する.また,経口補水が可能となった際は速やかに輸液を中止する.
    金原出版(株), Feb. 2021, 小児科, 62(2) (2), 130 - 135, Japanese

  • 明日から使える輸液療法の考え方 小児の維持輸液は低張液? それとも等張液?
    堀之内 智子, 野津 寛大
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 173 - 173, Japanese

  • 当科で経験した寡巨大糸球体症(Oligomeganephronia)の臨床病理学的検討
    北角 英晶, 忍頂寺 毅史, 増田 知佳, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 長野 智那, 榊原 菜々, 堀之内 智子, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 260 - 260, Japanese

  • Oxford分類を用いた小児IgA腎症・紫斑病性腎炎の臨床病理学的所見の比較
    島 友子, 中西 浩一, 田中 侑, 向山 弘展, 和田 卓三, 浜 武継, 佐藤 匡, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂, 鈴木 啓之
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 261 - 261, Japanese

  • Lowe症候群とDent disease-2における分子生物学的発症機序の解明
    榊原 菜々, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rosanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 忍頂寺 毅史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 284 - 284, Japanese

  • 異なる臨床像を呈したSLC4A1遺伝子による常染色体優性遠位尿細管性アシドーシスの姉弟例
    佐藤 望, 櫻谷 浩二, 長野 智那, 丘 宏逸, 吉田 登, 辻脇 篤志, 鈴木 恭子, 野津 寛大, 飯島 一誠, 大友 義之
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 285 - 285, Japanese

  • CLCN5遺伝子を含むX染色体微細欠失により発症したDent disease-1女性の2例
    榊原菜々, 野津寛大, 青砥悠哉, 長野智那, 堀之内智子, 忍頂寺毅史, 岡田絵里, 川口武彦, 今澤俊之, 稲垣徹史, 飯島一誠
    2021, 日本腎臓学会誌(Web), 63(4) (4)

  • 嚢胞性腎疾患の包括的遺伝子解析
    森貞直哉, 森貞直哉, 洪本加奈, 近藤淳, ROSSANTI Rini, 石河慎也, 青砥裕哉, 岡田絵里, 榊原奈々, 長野智那, 山村智彦, 堀之内智子, 貝藤裕史, 飯島一誠, 野津寛大
    2021, 日本人類遺伝学会大会プログラム・抄録集, 66th (CD-ROM)

  • 免疫複合体関連腎炎との鑑別を要したFrasier症候群の女児例
    津川浩二, 橋本峻, 佐藤理子, 相澤知美, 渡邊祥二郎, 田中完, 長野智那, 野津寛大, 城謙輔
    2021, 日本小児腎臓病学会雑誌(Web), 34(1) (1)

  • 発症8年後に再生検を行ったフィブロネクチン腎症の一例
    稲葉彩, 出崎緑, 出来沙織, 内村暢, 坂早苗, 平和伸仁, 千葉佐和子, 大谷方子, 伊藤秀一, 大坪裕美, 野津寛大, 城謙輔
    2021, 日本小児腎臓病学会雑誌(Web), 34(2) (2)

  • Seven patients of TSC2-PKD1 contiguous deletion syndrome diagnosed by MLPA
    森貞直哉, 森貞直哉, 花房宏昭, 山口宏, 岡田絵里, 洪本加奈, 長岡由修, 鈴村宏, 郭義胤, 福田智文, 下野九理子, 本郷裕斗, 貝藤裕史, 飯島一誠, 飯島一誠, 野津寛大
    2021, 日本小児遺伝学会学術集会プログラム・抄録集, 44th (CD-ROM)

  • 遺伝性疾患(遺伝病)を学ぶ Alport症候群
    野津 寛大
    Alport症候群は常染色体優性多発性嚢胞腎(ADPKD)に次いで2番目に発症頻度の高い遺伝性腎疾患である。しばしば腎不全へと進行する腎症、難聴、眼合併症を特徴とし、その遺伝形式にはX染色体連鎖型、常染色体優性、常染色体劣性の三つの遺伝様式がある。X染色体連鎖型男性患者および常染色体劣性Alport症候群患者は平均20〜30歳代で末期腎不全へと進行する一方、X染色体連鎖型女性および常染色体優性Alport症候群患者は平均60〜70歳代で末期腎不全へと進行する。現在まで特異的治療法は存在しないものの、ACE阻害薬およびアンギオテンシン受容体拮抗薬による治療で末期腎不全進行を遅延させることが可能であるとされている。(著者抄録)
    (株)メディカルドゥ, Jan. 2021, 遺伝子医学, 11(1) (1), 108 - 115, Japanese

  • 遺伝性腎疾患における遺伝学的検査方法の進歩
    野津 寛大, 森貞 直哉, 長野 智那, 堀之内 智子, 榊原 菜々, 山村 智彦, 飯島 一誠
    (有)科学評論社, Jan. 2021, 腎臓内科, 13(1) (1), 105 - 112, Japanese

  • 遺伝性疾患(遺伝病)を学ぶ Alport症候群
    野津 寛大
    (株)メディカルドゥ, Jan. 2021, 遺伝子医学, 11(1) (1), 108 - 115, Japanese

  • 小児AMR対策事業に協力する前の小児初期救急施設における内服抗菌薬処方割合と処方医師プロファイルとの関係
    木村 誠, 石橋 和人, 宍戸 亜由美, 笠井 正志, 野津 寛大, 石田 明人
    日本小児臨床薬理学会, Dec. 2020, 日本小児臨床薬理学会雑誌, 33(1) (1), 143 - 143, Japanese

  • 飯島 一誠, 佐古 まゆみ, 野津 寛大
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 43 - 43, Japanese

  • 野津 寛大
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 46 - 46, Japanese

  • 榊原 菜々, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rossanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 田中 亮二郎, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 76 - 76, Japanese

  • 石河 慎也, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 石森 真吾, 貝藤 裕史, 田中 亮二郎, 島 友子, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 77 - 77, Japanese

  • 長野 智那, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, 榊原 菜々, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 81 - 81, Japanese

  • 石河 慎也, 野津 寛大, 近藤 淳, 永井 貞之, 青砥 悠哉, 榊原 菜々, 長野 智那, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 82 - 82, Japanese

  • 榊原 菜々, 岡本 孝之, 野津 寛大, 佐藤 泰征, 林 麻子, 高橋 俊行, 上田 泰弘, 近藤 淳, 永井 貞之, 青砥 悠哉, 石河 慎也, Rossanti Rini, 長野 智那, 堀之内 智子, 山村 智彦, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 85 - 85, Japanese

  • 長岡 由修, 若林 知宏, 矢吹 郁美, 飯塚 裕典, 稲澤 奈津子, 木澤 敏毅, 伊藤 希美, 東舘 義仁, 小川 弥生, 石河 慎也, 長野 智那, 野津 寛大, 飯島 一誠, 川崎 幸彦
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 86 - 86, Japanese

  • 中村 実沙子, 神田 祥一郎, 梶保 祐子, 張田 豊, 森貞 直哉, 野津 寛大, 飯島 一誠, 岡 明
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 87 - 87, Japanese

  • 堀之内 智子, 長野 智那, 山村 智彦, 香山 雅子, 野津 寛大, 飯島 一誠, 荒瀬 尚
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 88 - 88, English

  • Rini Rossanti, 山村 智彦, 堀之内 智子, 長野 智那, 榊原 菜々, 石河 慎也, 青砥 悠哉, 近藤 淳, 永井 貞之, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 88 - 88, English

  • 永井 貞之, 山村 智彦, 近藤 淳, 青砥 悠哉, 石河 慎也, 榊原 菜々, 長野 智那, 堀之内 智子, 忍頂寺 毅史, 島 友子, 中西 浩一, 吉川 徳茂, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 107 - 107, Japanese

  • 稲葉 泰洋, 宮園 明典, 岡田 聡司, 河野 嘉文, 平林 雅子, 久野 敏, 野津 寛大
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 109 - 109, Japanese

  • 島 友子, 中西 浩一, 浜 武継, 向山 弘展, 佐藤 匡, 田中 侑, 和田 卓三, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 鈴木 啓之, 吉川 徳茂
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 109 - 109, Japanese

  • 河口 亜津彩, 荒木 義則, 榊原 菜々, 野津 寛大
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 123 - 123, Japanese

  • 荒木 義則, 河口 亜津彩, 森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 133 - 133, Japanese

  • 梶保 祐子, 神田 祥一郎, 張田 豊, 森貞 直哉, 野津 寛大, 飯島 一誠, 岡 明
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 138 - 138, Japanese

  • 石見 壮史, 北岡 太一, 山田 知絵子, 宮田 京, 中山 尋文, 武鑓 真司, 山本 賢一, 中野 由佳子, 藤原 誠, 大幡 泰久, 窪田 拓生, 山本 威久, 長野 智那, 野津 寛大, 飯島 一誠, 大薗 恵一
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 145 - 145, Japanese

  • 東 聡美, 出来 沙織, 雪澤 緑, 内村 暢, 稲葉 彩, 松野下 夏樹, 大熊 善彰, 大谷 方子, 野津 寛大, 飯島 一誠, 伊藤 秀一
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 147 - 147, Japanese

  • 森貞 直哉, 岡田 絵里, 今澤 俊之, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 148 - 148, Japanese

  • 内田 奈生, 菊池 敦生, 高橋 俊成, 松木 琢磨, 菅原 典子, 熊谷 直憲, 藤原 幾磨, 森貞 直哉, 野津 寛大, 飯島 一誠, 呉 繁夫
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 150 - 150, Japanese

  • 濱田 陸, 濱崎 祐子, 上村 治, 服部 元史, 中西 浩一, 丸山 彰一, 伊藤 秀一, 森貞 直哉, 野津 寛大, 張田 豊, 原田 涼子, 金子 徹治, 本田 雅敬, 石倉 健司
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 158 - 158, Japanese

  • 松村 千恵子, 菅谷 雅人, 升田 真依, 小林 雅代, 鵜野 裕一, 金本 勝義, 久野 正貴, 松野 大輔, 本間 澄恵, 大嶋 寛子, 福田 亜純, 岡田 絵里, 森貞 直哉, 野津 寛大, 末廣 真美子, 山口 淳一
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 160 - 160, Japanese

  • 村越 未希, 小椋 雅夫, 釜江 智佳子, 西 健太朗, 鈴木 竜太郎, 金森 透, 佐藤 舞, 長野 智那, 野津 寛大, 飯島 一誠, 亀井 宏一
    (一社)日本小児腎臓病学会, Dec. 2020, 日本小児腎臓病学会雑誌, 33(1Suppl.) (1Suppl.), 176 - 176, Japanese

  • 堀之内 智子, 野津 寛大, 飯島 一誠
    (株)東京医学社, Nov. 2020, 腎と透析, 89(5) (5), 846 - 849, Japanese

  • 【腎臓内科医が知っておくべき遺伝性腎疾患】Alport症候群
    山村 智彦, 野津 寛大
    (有)科学評論社, Nov. 2020, 腎臓内科, 12(5) (5), 467 - 473, Japanese

  • 家族性巣状分節性糸球体硬化症を疑われるもAlport症候群と判明し透析導入となった一例
    小田 康弘, 水野 裕基, 平松 里佳子, 早見 典子, 山内 真之, 諏訪部 達也, 星野 純一, 澤 直樹, 藤井 丈士, 野津 寛大, 乳原 善文
    (一社)日本透析医学会, Oct. 2020, 日本透析医学会雑誌, 53(Suppl.1) (Suppl.1), 388 - 388, Japanese

  • Aya Imafuku, Kandai Nozu, Naoki Sawa, Koichi Nakanishi, Yoshifumi Ubara
    Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning. These findings indicate a limitation in distinction between TBMN and ADAS. Diagnosis of AS is significant because it facilitates careful follow-up and early treatment, whereas diagnosis of TBMN can underestimate the risk of ESRD. However, some experts are against using the term ADAS as the phenotypes of heterozygous variants vary from no urinary abnormality to ESRD, even between family members with the same mutations, indicating that unknown secondary factors may play a large role in the disease severity. These diagnostic difficulties result in significant confusion in clinical settings. Moreover, recent studies revealed that the number of patients with chronic kidney disease caused by these gene mutations is far higher than previously thought. The aim of this article is to review differing opinions regarding the diagnosis of heterozygous COL4A3 or COL4A4 variants, and to highlight the importance for nephrologists to recognize this disease, and the importance of the need to reclassify this disease to minimize the current confusion.
    Springer, 01 Aug. 2020, Clinical and Experimental Nephrology, 24(8) (8), 651 - 656, English
    Book review

  • 手塚 優子, 鎌田 ゆきえ, 加賀田 敬郎, 石井 榮一, 野津 寛大, 中西 啓太, 飯島 一誠
    (一社)日本小児腎臓病学会, Apr. 2020, 日本小児腎臓病学会雑誌, 33(1) (1), 86 - 87, Japanese

  • 長尾 佳樹, 石原 正行, 石塚 喜世伸, 三浦 健一郎, 服部 元史, 長野 智那, 野津 寛大, 飯島 一誠, 藤枝 幹也
    (一社)日本小児腎臓病学会, Apr. 2020, 日本小児腎臓病学会雑誌, 33(1) (1), 105 - 105, Japanese

  • RNを科学する-ともに考えようRNの管理- VURと遺伝子異常
    森貞 直哉, 野津 寛大, 飯島 一誠
    日本逆流性腎症フォーラム, Feb. 2020, 日本逆流性腎症フォーラムプログラム・抄録集, 28回, 14 - 14, Japanese

  • Dent病に合併した薬剤性の急性尿細管間質性腎炎の1例
    財津 亜友子, 田中 征治, 江﨑 拓也, 長野 智那, 榊原 菜々, 野津 寛大, 飯島 一誠
    東京 : 日本小児腎不全学会, 2020, 日本小児腎不全学会雑誌 = Journal of Japanese Society for Pediatric Renal Failure, 40, 191 - 194, Japanese

  • アルドステロン高値により診断に至った早産児の偽性低アルドステロン症1型の1例
    角谷哲基, 牟禮岳男, 河野一誠, 武田紗季, 住吉倫卓, 榎本真由子, 藤坂方葉, 水野洋介, 下村真由美, 西野昌光, 野津寛大, 飯島一誠, 吉井勝彦
    2020, 日本小児科学会雑誌, 124(6) (6)

  • 遺伝子検査で診断に至ったX連鎖型Alport症候群の1例
    滝口陽介, 廣坂雄介, 藤野隆弘, 大町将司, 上田久巳, 潮正輝, 森田善方, 野津寛大, 川野充弘, 霍田裕明
    2020, 滋賀医学, 42

  • Dent disease-2の女児例に関する初めての報告およびその発症機序の解明
    榊原菜々, 岡本孝之, 野津寛大, 佐藤泰征, 林麻子, 高橋俊行, 上田泰弘, 近藤淳, 永井貞之, 青砥悠哉, 石河慎也, ROSSANTI Rini, 長野智那, 堀之内智子, 山村智彦, 飯島一誠
    2020, 日本小児腎臓病学会雑誌(Web), 33(1) (1)

  • 第2子に偽性低アルドステロン症を認め、第1子にも高レニン・高アルドステロン血症を認めた二絨毛膜二羊膜双胎例
    市川 裕太, 藤岡 一路, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠
    (株)東京医学社, Dec. 2019, 周産期医学, 49(12) (12), 1675 - 1678, Japanese

  • Alport症候群モデルマウスにおけるエクソンスキッピング療法の有効性の検討
    山村 智彦, 野津 寛大, 堀之内 智子, 南川 将吾, 足立 朝美, 寺川 真紀, 永瀬 弘之, 高石 巨澄, 大西 朗之, 小路 貴生, 小泉 誠, 神田 祥一郎, 張田 豊, 嘉村 美里, 甲斐 広文, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2019, 日本小児腎臓病学会雑誌, 32(2) (2), 138 - 138, Japanese

  • 種々の病態における水電解質異常 診断に苦慮し、遺伝子検査にて確定診断に至った低K血症の1例
    清水 真央, 後藤 俊介, 原 明子, 大田 健人, 野津 寛大, 藤井 秀毅, 西 愼一
    臨床体液研究会, Sep. 2019, 臨床体液, 46, 3 - 3, Japanese

  • 出生後初回の採血で著明な高K血症を呈した尿路奇形を伴わない続発性偽性低アルドステロン症の1新生児例
    市川 裕太, 藤岡 一路, 芦名 満理子, 阿部 真也, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠
    在胎36週3日、出生体重2,464g、Apgar Score 9/9点、緊急帝王切開で出生した男児。早産、低出生体重のため入院となった。入院後初回の血液検査で、高K血症(7.4mEq/L)を認めた。腹部エコーで尿路奇形や水腎症は認めず、尿培養は陰性で、代謝性アシドーシスは認めなかったが、動脈ライン採血を含む複数回の再検でも高K血症を認めたため、日齢0よりグルコン酸Ca水和物注射に加えて、グルコース・インスリン療法を行い、高K血症は速やかに軽快した。精査のため提出した血中アルドステロン濃度3,680pg/mL、レニン活性>20ng/mL/hrと上昇を認めたことより、続発性偽性低アルドステロン症と診断した。退院後の検査で、ミネラルコルチコイド受容体遺伝子に変異は認めなかった。本症例のように尿路奇形の合併を認めない場合でも、出生直後の高K血症の原因として続発性偽性低アルドステロン症を念頭におく必要がある。(著者抄録)
    (株)日本小児医事出版社, Aug. 2019, 小児科臨床, 72(8) (8), 1030 - 1034, Japanese

  • Alport症候群モデルマウスにおけるエクソンスキッピング療法の有効性の検討
    山村 智彦, 野津 寛大, 堀之内 智子, 南川 将吾, 足立 朝美, 寺川 真紀, 永瀬 弘之, 高石 巨澄, 大西 朗之, 小路 貴生, 小泉 誠, 神田 祥一郎, 張田 豊, 嘉村 美里, 甲斐 広文, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 90 - 90, Japanese

  • WT1遺伝子KTS変異による免疫複合体腎炎の発症機序の検討
    松岡 大輔, 野田 俊輔, 日高 義彦, 下条 久志, 宮本 強, 塚口 裕康, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2019, 日本小児腎臓病学会雑誌, 32(1Suppl.) (1Suppl.), 182 - 182, Japanese

  • Genetic disease of the kidney and the urinary tract
    長野 智那, 野津 寛大, 飯島 一誠
    科学評論社, May 2019, 腎臓内科・泌尿器科 = Nephrology & urology, 9(5) (5), 425 - 429, Japanese

  • 6つのネフローゼ遺伝子変異が描く治療可能な病態パスウェイ
    菊池 敦生, 工藤 宏紀, 新堀 哲也, 熊谷 直憲, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 濱平 陽史, 小林 靖子, 滝沢 琢己, 青木 洋子, 飯島 一誠, 呉 繁夫
    (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 283 - 283, Japanese

  • 6つのネフローゼ遺伝子変異が描く治療可能な病態パスウェイ
    菊池 敦生, 工藤 宏紀, 新堀 哲也, 熊谷 直憲, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 濱平 陽史, 小林 靖子, 滝沢 琢己, 青木 洋子, 飯島 一誠, 呉 繁夫
    (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 283 - 283, Japanese

  • 頭痛・全身倦怠感を主訴に診断されたGitelman症候群の姉弟例
    中島久和, 幸道和樹, 森元英周, 野津寛大
    2019, 日本小児内分泌学会学術集会プログラム・抄録集, 53rd

  • 診断に苦慮し,遺伝子検査にて確定診断に至った低K血症の1例
    清水真央, 後藤俊介, 原明子, 大田健人, 野津寛大, 藤井秀毅, 西愼一
    2019, 臨床体液(Web), 46

  • 【難しくない 小児腎領域の難病診療】 小児腎領域の小児慢性特定疾病・指定難病 バーター(Bartter)症候群・ギッテルマン(Gitelman)症候群
    野津 寛大
    ●Bartter症候群(BS)、Gitelman症候群(GS)は低カリウム血症、代謝性アルカローシスなどを特徴とする先天性尿細管機能障害に伴う症候群である。●1977年に厚生労働省により作成された診断基準はあるものの、遺伝子診断を含めた新診断基準の策定が急務である。●同病態は利尿薬や緩下薬の常用、やせ等の二次的要因や、Dent病、線維性嚢胞症、先天性クロル下痢症、家族性高カルシウム尿性低カルシウム血症、Renal cystic and diabetes syndromeなど他の先天性疾患でも起こし得るので正確な診断が必要である。(著者抄録)
    (株)診断と治療社, Dec. 2018, 小児科診療, 81(12) (12), 1723 - 1729, Japanese

  • 尿細管性アシドーシス1、2型の鑑別はどのように行われるか? 現在は負荷試験なしで遺伝子診断をオーダーすることが多い
    野津 寛大
    (株)日本医事新報社, Oct. 2018, 日本医事新報, (4930) (4930), 61 - 62, Japanese

  • 【腎移植-最新の知見】 原因疾患に応じた治療戦略 WT1関連腎炎の術前・術後管理
    野津 寛大
    (株)東京医学社, Oct. 2018, 腎と透析, 85(4) (4), 568 - 572, Japanese

  • 【小児腎・泌尿器疾患update】 遺伝性尿細管機能異常症
    南川 将吾, 野津 寛大, 飯島 一誠
    ＜文献概要＞近年,次世代シークエンサー登場などの遺伝子解析技術の向上により,小児腎臓病と遺伝子異常との密接な関連性が明らかとなった.とくに腎尿細管においては多くの膜輸送体が存在しており,これらの機能に影響を与え尿細管機能異常症を起こす遺伝子は非常に多いことがわかってきた.いまだ発見されていない原因遺伝子や病態生理の不明な疾患も多数あるが,現時点で判明している疾患ごとの原因遺伝子とその臨床的特徴,診断におけるポイントを概説する.
    金原出版(株), Sep. 2018, 小児科, 59(10) (10), 1409 - 1417, Japanese

  • Alport症候群における分子生物学的治療法開発の現状
    野津寛大
    31 Jul. 2018, 日本小児腎不全学会雑誌, 38, 7‐10, Japanese

  • COQ6遺伝子の複合ヘテロ接合体変異を同定した乳児ネフローゼ症候群の1例
    濱田 詩織, 平松 泰好, 大竹 直人, 佐藤 逸美, 中山 加奈子, 八鍬 聡, 那須 敬, 田原 泰夫, 植竹 公明, 岡本 孝之, 佐藤 泰征, 林 麻子, 高橋 俊行, 野津 寛大, 深澤 雄一郎, 久野 敏
    (公社)日本小児科学会, Jul. 2018, 日本小児科学会雑誌, 122(7) (7), 1256 - 1257, Japanese

  • 片腎摘なしでネフローゼ期の管理を行っているフィンランド型先天性ネフローゼ症候群の男児例
    一岡 聡子, 坂井 智行, 角 恵理子, 増田 俊樹, 奥田 雄介, 澤井 俊宏, 中西 啓太, 野津 寛大, 飯島 一誠
    片腎摘を行わずネフローゼ期を管理しているフィンランド型ネフローゼ症候群(CNF)の男児例を経験した。生後3週時に他院で先天性ネフローゼ症候群と診断され、生後3ヵ月時に当院へ転院した。当初は頻回のアルブミン(Alb)輸注が必要であったが、enalaprilとindomethacinを併用しAlb輸注を中止できた。生後7ヵ月時に外来管理へ移行し、1歳現在まで成長発達は良好である。ACE阻害薬、indomethacin投与を初期に試行し、その反応性に応じて腎摘の適応を判断することは、軽症例において腎摘を回避できる可能性があると考えられた。本症例の遺伝子検査ではNPHS1の複合ヘテロ接合体変異が判明したが表現型との関連は明らかでなく、遺伝子変異と表現型の関連についてはさらなる検討が望まれる。(著者抄録)
    日本小児腎不全学会, Jul. 2018, 日本小児腎不全学会雑誌, 38, 178 - 181, Japanese

  • ゲノム情報を臨床へ 遺伝性腎疾患へのアプローチ バイオサイエンスデータベースを使った解析手法
    野津 寛大
    ＜文献概要＞近年の遺伝子解析技術の進歩に伴い,多数の遺伝子を同時にスクリーニングする網羅的遺伝子解析法が普及した.それに伴い,一度の解析で多数の遺伝子の情報が得られることとなった.しかし,それらの検出された遺伝子の情報から,患者の病気の原因となる情報のみを抽出する作業には困難と責任を伴う.なかでも,患者の病気の原因と考えられる遺伝子にミスセンス変異やスプライシングに影響を与え得る塩基の変異を検出した場合にはその病原性の判定は非常に困難であり,そのような場合にはバイオサイエンスデータベースの有効活用が必須である.本稿では実際に有用なバイオサイエンスデータベースに関してその活用法につき解説する.
    金原出版(株), Jul. 2018, 小児科, 59(8) (8), 1197 - 1202, Japanese

  • COQ6遺伝子の複合ヘテロ接合体変異を同定した乳児ネフローゼ症候群の1例
    濱田 詩織, 平松 泰好, 大竹 直人, 佐藤 逸美, 中山 加奈子, 八鍬 聡, 那須 敬, 田原 泰夫, 植竹 公明, 岡本 孝之, 佐藤 泰征, 林 麻子, 高橋 俊行, 野津 寛大, 深澤 雄一郎, 久野 敏
    (公社)日本小児科学会, Jul. 2018, 日本小児科学会雑誌, 122(7) (7), 1256 - 1257, Japanese

  • 野津寛大
    01 Jul. 2018, 小児科, 59(8) (8), 1197‐1202, Japanese

  • 高血圧を呈さず高度蛋白尿が遷延した溶連菌感染後急性糸球体腎炎の1例
    藤村 順也, 貝藤 裕史, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 野津 寛大, 飯島 一誠
    症例は8歳の女児で、肉眼的血尿を主訴に前医を受診した。1kg(+5%)の体重増加と上眼瞼の浮腫を認めたが、高血圧はなかった。肉眼的血尿と高度蛋白尿に加え、腎機能障害、低補体血症、低アルブミン血症を認めた。APSGNとして保存的加療が開始されたが、腎機能障害と乏尿が改善せず当院に転院となった。転院後もネフローゼレベルの蛋白尿と腎機能障害が遷延したため第14病日に腎生検を行った。光顕所見ではびまん性の管内細胞増殖と係蹄壁の二重化およびメサンギウム細胞増殖を認め、また40%の糸球体に線維細胞性半月体を認めた。免疫染色でC3の顆粒状沈着と電子顕微鏡所見でhumpを認めたことから、APSGNと確定診断した。メチルプレドニゾロンパルス療法を施行したところ発症後1ヵ月で腎機能は正常化し、また3ヵ月で尿蛋白は陰性化した。転院後も高血圧を呈することはなかった。APSGNにおける高血圧の発症機序は一般に、ナトリウム・水貯留によるhypervolemiaで説明される。本症例では経過を通じ溢水所見を呈したことはなく、これは血圧の推移と矛盾しない。しかしその一方で、腎機能の推移や腎病理所見からは腎性の要素で高血圧を呈する危険性も十分に考えられた。APSGNではまれとされる高度蛋白尿が病態を修飾した可能性も考えられた。溢水所見や血圧上昇を認めないAPSGNであっても体液量管理は慎重に行う必要がある。(著者抄録)
    日本小児高血圧研究会, Jun. 2018, 日本小児高血圧研究会誌, 15(1) (1), 21 - 25, Japanese

  • 遺伝学的検査 2.単一遺伝子疾患 2)Alport症候群
    野津寛大
    30 May 2018, 腎と透析, 84, 358‐360, Japanese

  • COQ6遺伝子の複合ヘテロ接合体変異を同定した乳児ネフローゼ症候群の一例
    濱田 詩織, 岡本 孝之, 野津 寛大, 中西 啓太, 飯島 一誠, 佐藤 泰征, 林 麻子, 高橋 俊行, 八鍬 聡, 植竹 公明, 深澤 雄一郎, 久野 敏, 有賀 正
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 102 - 102, Japanese

  • 堀之内 智子, Jia Xiaoyuan, 人見 祐基, 石倉 健司, 亀井 宏一, 濱田 陸, 郭 義胤, 藤丸 季可, 岡本 孝之, 大和田 葉子, 田中 亮二郎, 後藤 芳充, 貝藤 裕史, 野津 寛大, 徳永 勝士, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 155 - 155, Japanese

  • 【腎と透析ベッドサイド検査事典】 (第12章)遺伝学的検査 単一遺伝子疾患 Alport症候群
    野津 寛大
    (株)東京医学社, May 2018, 腎と透析, 84(増刊) (増刊), 358 - 360, Japanese

  • 3歳児検尿での軽微な蛋白尿を契機に診断した常染色体優性遠位尿細管性アシドーシス
    藤原 香緒里, 道上 敏美, 山村 なつみ, 里村 憲一, 木村 三郎, 松野下 夏樹, 野津 寛大, 飯島 一誠, 山本 勝輔
    (公社)日本小児科学会, May 2018, 日本小児科学会雑誌, 122(5) (5), 896 - 902, Japanese

  • 低身長を契機に診断に至ったGitelman症候群の2例
    藤村 順也, 野津 寛大, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    日本小児体液研究会, May 2018, 日本小児体液研究会誌, 10, 67 - 72, Japanese

  • ネフローゼ症候群の病因と病態 ネフローゼ症候群の病因としての遺伝子異常
    野津 寛大, 中西 啓太, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 73 - 73, Japanese

  • In vitro実験系を用いたCOL4A5 intron変異の病原性の検討
    堀之内 智子, 山村 智彦, 榊原 菜々, 長野 智那, 藤村 順也, 中西 啓太, 南川 将吾, 貝藤 裕史, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 99 - 99, Japanese

  • 次世代シークエンサーによるネフロン癆関連シリオパチーの包括的遺伝子解析
    榊原 菜々, 森貞 直哉, 長野 智那, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 山村 智彦, 貝藤 裕史, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 100 - 100, Japanese

  • Copy Number Variations解析により遺伝学的診断が臨床診断と異なる結果を得た4症例の検討
    長野 智那, 野津 寛大, 森貞 直哉, 松村 千恵子, 榊原 菜々, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 101 - 101, Japanese

  • COQ6遺伝子の複合ヘテロ接合体変異を同定した乳児ネフローゼ症候群の一例
    濱田 詩織, 岡本 孝之, 野津 寛大, 中西 啓太, 飯島 一誠, 佐藤 泰征, 林 麻子, 高橋 俊行, 八鍬 聡, 植竹 公明, 深澤 雄一郎, 久野 敏, 有賀 正
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 102 - 102, Japanese

  • NPHP1ホモ全欠失を合併した原発性アルドステロン血症の一例
    森 一越, 鈴木 繁, 川村 研, 森貞 直哉, 野津 寛大
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 123 - 123, Japanese

  • In vitro splicing assayを用いたFrasier症候群の臨床遺伝学的検討
    辻 ゆり佳, 山村 智彦, 野津 寛大, 榊原 菜々, 長野 智那, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 147 - 147, Japanese

  • 8歳でステロイド抵抗性ネフローゼ症候群を発症し後にNPHS1複合ヘテロ接合体変異が判明した女児例
    亀井 宏一, 野津 寛大, 中西 啓太, 長野 智那, 奥津 美夏, 石和 翔, 西 健太朗, 松村 壮史, 佐藤 舞, 小椋 雅夫, 佐古 まゆみ, 伊藤 秀一, 飯島 一誠, 石倉 健司
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 154 - 154, Japanese

  • 無症候性蛋白尿を契機に診断されたステロイド抵抗性ネフローゼ症候群の原因遺伝子症例の検討
    権田 裕亮, 櫻谷 浩志, 西野 智彦, 富井 祐治, 掛川 大輔, 村上 仁彦, 野津 寛大, 中西 浩一, 飯島 一誠, 藤永 周一郎
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 154 - 154, Japanese

  • ゲノムワイド関連解析による小児特発性ネフローゼ症候群のrisk haplotype同定
    堀之内 智子, Jia Xiaoyuan, 人見 祐基, 石倉 健司, 亀井 宏一, 濱田 陸, 郭 義胤, 藤丸 季可, 岡本 孝之, 大和田 葉子, 田中 亮二郎, 後藤 芳充, 貝藤 裕史, 野津 寛大, 徳永 勝士, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 155 - 155, Japanese

  • 尿中CD80の腎疾患診断マーカーとしての有用性の検討
    南川 将吾, 野津 寛大, 前田 真吾, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 藤村 順也, 山村 智彦, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 156 - 156, Japanese

  • 無症候性蛋白尿を契機に発見されたTRPC6遺伝子変異による巣状糸球体硬化症の女児例
    鈴木 博乃, 山田 拓司, 水野 奈々, 武田 理沙, 石本 明香里, 吉田 明生, 福田 恵子, 側島 健宏, 横井 暁子, 小林 悟, 神岡 直美, 濱嶋 直樹, 伊藤 康彦, 村松 幹司, 鈴木 悟, 野津 寛大
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 157 - 157, Japanese

  • 男性腎不全の家族歴からネフロン癆関連シリオパチーの診断に至った3歳男児例
    和田 卓三, 島 友子, 田中 侑, 佐藤 匡, 浜 武継, 向山 弘展, 鈴木 啓之, 森貞 直哉, 野津 寛大, 飯島 一誠, 中西 浩一
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 166 - 166, Japanese

  • 遺伝学的検査により確定診断され、次子の出生前診断が検討された遺伝性腎疾患の2家系
    加納 優治, 西 健太朗, 石和 翔, 奥津 美夏, 松村 壮史, 佐藤 舞, 小椋 雅夫, 亀井 宏一, 福原 康之, 野津 寛大, 池田 真理子, 倉橋 浩樹, 石倉 健司
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 168 - 168, Japanese

  • 小児silent lupus nephritisに関する臨床病理学的検討
    島 友子, 中西 浩一, 浜 武継, 田中 侑, 佐藤 匡, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 鈴木 啓之, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 170 - 170, Japanese

  • 常染色体劣性型が疑われたが、遺伝子解析の結果X連鎖型Alport症候群と診断された1例
    永田 裕子, 日高 優子, 田村 博, 河野 智康, 永野 幸治, 師井 裕記朗, 野津 寛大, 飯島 一誠, 仲里 仁史
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 184 - 184, Japanese

  • 溶連菌感染後急性糸球体腎炎罹患後に急速に腎機能障害が進行し末期腎不全に至ったAlport症候群の高校生男児
    荒木 義則, 河口 亜津彩, 野津 寛大
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 186 - 186, Japanese

  • SLC4A1遺伝子による遠位尿細管性アシドーシスの姉妹例
    山田 祐子, 横山 浩己, 北本 晃一, 河場 康郎, 岡田 晋一, 野津 寛大, 飯島 一誠, 神崎 晋
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 199 - 199, Japanese

  • 成長ホルモン補充療法中に、低K血症、手足の痺れからGitelman症候群と診断された一例
    溝端 理恵, 岡 政史, 佐藤 忠司, 在津 正文, 野津 寛大, 飯島 一誠, 大塚 泰史, 松尾 宗明
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 200 - 200, Japanese

  • Gitelman症候群185例における臨床的特徴に関する検討
    藤村 順也, 野津 寛大, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 200 - 200, Japanese

  • 不完全型Denys-Drash症候群が疑われる新規遺伝子変異を示した1例
    西村 真直, 武市 実奈, 郭 義胤, 鈴木 秀一, 虫本 雄一, 都 健一, 野津 寛大
    (一社)日本小児腎臓病学会, May 2018, 日本小児腎臓病学会雑誌, 31(1Suppl.) (1Suppl.), 209 - 209, Japanese

  • 慢性硬膜下血腫を契機にGitelman症候群と診断された一例
    森田 皓貴, 伊藤 祐一, 田中 章仁, 野津 寛大
    (一社)日本透析医学会, May 2018, 日本透析医学会雑誌, 51(Suppl.1) (Suppl.1), 699 - 699, Japanese

  • 未診断疾患における網羅的ゲノム解析時代の遺伝カウンセリング 小児慢性腎臓病(CKD)の原因遺伝子解析と遺伝カウンセリング
    森貞 直哉, 野津 寛大, 飯島 一誠
    日本遺伝カウンセリング学会, Apr. 2018, 日本遺伝カウンセリング学会誌, 39(1) (1), 31 - 36, Japanese

  • OFD1ヘミ接合性変異を認めたネフロン癆関連シリオパチーの1男児例
    森貞 直哉, 清水 順也, 庄司 朱美, 池田 真理子, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 814 - 814, Japanese

  • 治療方針の決定に疾患パネル解析を用いたステロイド抵抗性ネフローゼ症候群の1例
    長野 智那, 貝藤 裕史, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 山村 智彦, 野津 寛大, 神吉 直宙, 濱平 陽史, 飯島 一誠
    (公社)日本小児科学会, Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 814 - 815, Japanese

  • 【小児の治療指針】 腎・尿路 Alport症候群
    山村 智彦, 野津 寛大, 飯島 一誠
    (株)診断と治療社, Apr. 2018, 小児科診療, 81(増刊) (増刊), 777 - 779, Japanese

  • 矮小陰茎、停留精巣、高度蛋白尿を契機に不全型Denys-Drash症候群が疑われた1例
    鈴木 秀一, 虫本 雄一, 河野 敦子, 都 研一, 武市 実奈, 西村 真直, 郭 義胤, 野津 寛大
    (一社)日本内分泌学会, Apr. 2018, 日本内分泌学会雑誌, 94(1) (1), 433 - 433, Japanese

  • 腎臓病領域における希少疾患と指定難病 小児希少疾患の遺伝子解析の意義
    野津 寛大, 森貞 直哉, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 285 - 285, Japanese

  • X染色体連鎖型Alport症候群男性患者341名の臨床遺伝学的検討
    山村 智彦, 野津 寛大, 長野 智那, 榊原 菜々, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 貝藤 裕史, 中西 浩一, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 336 - 336, Japanese

  • Gitelman症候群185例における臨床的特徴に関する検討
    藤村 順也, 野津 寛大, 長野 智那, 榊原 菜々, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 次世代シークエンサー解析データを用いたpair解析により診断に至った遺伝性腎疾患例に関する検討
    長野 智那, 野津 寛大, 森貞 直哉, 榊原 菜々, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 抗変異MUC1抗体によるADTKD-MUC1診断の可能性
    岡田 絵里, 森貞 直哉, 森 維久郎, 山田 亜純, 上原 正樹, 岡島 真里, 川口 武彦, 首村 守俊, 北村 博司, 野津 寛大, 飯島 誠一, 今澤 俊之
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 337 - 337, Japanese

  • 多様な表現型を示したピアソン症候群における遺伝学的・分子生物学的検討
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 貝藤 裕史, 平野 大志, 原田 涼子, 濱田 陸, 西山 慶, 稲垣 徹史, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 338 - 338, Japanese

  • ゲノムワイド関連解析による小児特発性ネフローゼ症候群のrisk haplotype同定
    堀之内 智子, 野津 寛大, 石倉 健司, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 344 - 344, Japanese

  • ステロイド抵抗性ネフローゼ症候群における網羅的遺伝子診断体制の構築
    中西 啓太, 野津 寛大, 榊原 菜々, 長野 智那, 藤村 順也, 堀之内 智子, 南川 将吾, 山村 智彦, 貝藤 裕史, 島 友子, 中西 浩一, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 344 - 344, Japanese

  • 遺伝子解析が診断に有用であったLMX1B関連腎症の1家系
    尾崎 太郎, 下野 愛子, 大西 啓右, 藤田 拓朗, 守時 政宏, 西島 陽子, 祖父江 理, 串田 吉生, 野津 寛大, 南野 哲男
    (一社)日本腎臓学会, Apr. 2018, 日本腎臓学会誌, 60(3) (3), 421 - 421, Japanese

  • 未診断疾患における網羅的ゲノム解析時代の遺伝カウンセリング 小児慢性腎臓病(CKD)の原因遺伝子解析と遺伝カウンセリング
    森貞 直哉, 野津 寛大, 飯島 一誠
    日本遺伝カウンセリング学会, Apr. 2018, 日本遺伝カウンセリング学会誌, 39(1) (1), 31 - 36, Japanese

  • X染色体不活化とDent病
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 貝藤 裕史, 飯島 一誠
    X染色体連鎖型腎疾患における女性症例の重症化には、X染色体不活化率の偏り(skewed X)が主な原因の一つと考えられている。X染色体不活化の解析法において、従来のHUMARA法では、i)変異遺伝子を直接測定しているものではなく、ii)ゲノムレベルの解析にとどまるという欠点があった。しかし、近年の次世代シークエンサー(NGS)の登場によりこれらの弱点を克服したRNA-Seq法による不活化解析が可能となった。Dent病は稀なX連鎖型遺伝性腎疾患であり、女性においては軽症となることが一般的であるが、一部重度の表現型を呈する症例も存在する。この原因についてはX染色体不活化の関連が疑われるが、未だそれを明確に示した報告は無く、HUMARA法やNGSを用いたX染色体不活化解析の報告が待たれる。(著者抄録)
    発達腎研究会, Apr. 2018, 発達腎研究会誌, 26(1) (1), 8 - 10, Japanese

  • 【腎泌尿器領域における個別化医療・精密医療】 ゲノム医療で変わる小児腎領域
    野津 寛大
    (有)科学評論社, Feb. 2018, 腎臓内科・泌尿器科, 7(2) (2), 148 - 153, Japanese

  • 次世代シークエンサーを用いたAlport症候群の網羅的診断法の確立
    山村 智彦, 野津 寛大, 長野 智那, 榊原 菜々, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 256 - 256, Japanese

  • Gitelman症候群の臨床的特徴に関する検討
    藤村 順也, 野津 寛大, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 257 - 257, Japanese

  • 尿中CD80の腎疾患診断マーカーとしての有用性の検討
    南川 将吾, 野津 寛大, 前田 真吾, 榊原 菜々, 長野 智那, 中西 啓太, 堀之内 智子, 藤村 順也, 山村 智彦, 貝藤 裕史, 飯島 一誠
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 285 - 285, Japanese

  • 小児IgA腎症における蛋白尿再燃因子の検討
    島 友子, 中西 浩一, 浜 武継, 田中 侑, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂, 鈴木 啓之
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 307 - 307, Japanese

  • 成長ホルモン補充療法中に診断に至ったGitelman症候群の一例(A case of Gitelman syndrome complicated with growth hormone deficiency)
    岡 政史, 溝端 理恵, 冨野 広道, 中村 拓自, 稲田 由紀子, 溝口 達弘, 西川 小百合, 野津 寛大, 飯島 一誠, 在津 正文, 佐藤 忠司
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 395 - 395, English

  • 急速に末期腎不全に至ったACTN4新規遺伝子変異を伴うFSGSの13歳男子
    櫻谷 浩志, 藤永 周一郎, 西野 智彦, 富井 祐治, 掛川 大輔, 中西 啓太, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 396 - 396, Japanese

  • NUP107の複合ヘテロ変異を認めた無症候性蛋白尿の3歳女児
    亀井 宏一, 奥津 美夏, 石和 翔, 西 健太朗, 松村 壮史, 佐藤 舞, 小椋 雅夫, 中西 啓太, 野津 寛大, 飯島 一誠, 石倉 健司
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 396 - 396, Japanese

  • TTC21B遺伝子の複合ヘテロ接合性変異を認めた多発性嚢胞腎の一例
    日比野 聡, 森貞 直哉, 松田 百代, 西村 竜哉, 加賀田 敬郎, 内田 博之, 田中 一樹, 野津 寛大, 飯島 一誠, 藤田 直也
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 397 - 397, Japanese

  • 腎動脈ではなく腎末梢動脈狭窄による腎血管性高血圧症と診断し得たもやもや病の1例
    神田 杏子, 稲熊 洋祐, 中川 拓, 長野 智那, 貝藤 裕史, 野津 寛大, 飯島 一誠, 田中 亮二郎
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 445 - 445, Japanese

  • くる病症状、低身長を呈した常染色体優性遠位尿細管性アシドーシスの一例
    内藤 由紀, 井上 翔太郎, 藤原 絢子, 明神 翔太, 坂田 千恵, 中迫 正祥, 神吉 直宙, 中川 卓, 高見 勇一, 藤田 秀樹, 久呉 真章, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 446 - 446, Japanese

  • ドナー選定を考慮した遺伝子診断でBOR症候群と診断された一例
    韓蔚, 寺下真帆, 谷澤雅彦, 長谷川正宇, 市川大介, 矢萩浩一, 佐々木秀郎, 丸井祐二, 力石辰也, 飯島一誠, 野津寛大, 柴垣有吾
    2018, 日本臨床腎移植学会プログラム・抄録集, 51st, 145, Japanese

  • 遺伝子検査で原発性オキサローシスを除外した1例
    角浩史, 谷澤雅彦, 長谷川正宇, 寺下真帆, 白井小百合, 佐々木秀郎, 丸井祐二, 力石辰也, 飯島一誠, 野津寛大, 柴垣有吾
    2018, 日本臨床腎移植学会プログラム・抄録集, 51st, 247, Japanese

  • 堀之内 智子, 野津 寛大, 飯島 一誠
    遺伝性リン代謝異常症や遺伝性マグネシウム代謝異常症は多岐にわたり,数々の原因遺伝子が同定されている.遺伝性高リン血症はFGF23の作用不全やPTHの作用不全を病態の首座とし,遺伝性低リン血症はFGF23の作用過剰や1,25(OH)2Dの作用不全,近位尿細管障害を病態の首座とする.また,遺伝性マグネシウム代謝異常症は尿細管におけるマグネシウムの再吸収調節機構異常が原因である.一般的に各疾患の頻度は低く,表現型にも多様性を認めることから,臨床診断が困難なことも多い.近年,次世代シークエンサーが各方面で応用されており,遺伝性リン代謝異常症や遺伝性マグネシウム代謝異常症においても遺伝子診断が比較的容易となる可能性が考えられる.(著者抄録)
    (株)日本メディカルセンター, Jan. 2018, 腎と骨代謝, 31(1) (1), 37 - 43, Japanese

  • 低身長を主訴に発見されたGitelman症候群の姉妹例
    川村 研, 篠崎 みずき, 鈴木 繁, 森 一越, 野津 寛大
    (公社)日本小児科学会, Dec. 2017, 日本小児科学会雑誌, 121(12) (12), 2026 - 2026, Japanese

  • 【知っておきたい「子どもの脱水と輸液管理」】 正しい輸液療法のあり方
    野津 寛大
    ＜Point＞▼輸液療法とは、体内の水分量および組成を正常に保つため、水分や電解質、糖分などを直接静脈内に補充する治療法である▼臨床においては、(1)何らかの原因により不足した体内の水分や電解質を補うための輸液[補充輸液(deficit fluid)]、(2)体内の恒常状態(ホメオスタシス)を維持するための輸液[維持輸液(maintenance fluid)]、に分類される▼補充輸液においては、体内の水分欠乏量を正確に判定し、等張液を用いて補う必要がある▼入院中の小児患者の多くはnon-osmotic stimuliによりバゾプレシン(AVP)の分泌亢進状態であるため、低張液の投与により医原性低ナトリウム(Na)血症の発症リスクが高くなる▼小児の維持輸液において憂慮すべき最優先事項は、低Na血症の発症を未然に防ぐことである。その上で、患者の注意深い観察の元、輸液製剤の種類および投与量を決定する必要がある(著者抄録)
    (株)日本医事新報社, Nov. 2017, 日本医事新報, (4880) (4880), 38 - 44, Japanese

  • 3型Bartter症候群(3型BS)の2例とGitelman症候群(GS)の2例:臨床診断の限界について
    三浦 真理子, 加納 優治, 伊東 藍, 前川 貴伸, 小椋 雅夫, 亀井 宏一, 野津 寛大, 窪田 満, 石黒 精, 石倉 健司
    (公社)日本小児科学会, Nov. 2017, 日本小児科学会雑誌, 121(11) (11), 1898 - 1898, Japanese

  • 【小児臨床検査のポイント2017】 腎機能検査 尿細管機能検査 遠位尿細管・集合管機能検査 尿濃縮能、TTKG、フロセミド負荷試験、塩化アンモニウム負荷試験
    野津 寛大
    (株)東京医学社, Nov. 2017, 小児内科, 49(増刊) (増刊), 256 - 258, Japanese

  • エクソンスキッピング療法によるアルポート症候群特異的治療法の開発
    庄野 朱美, 野津 寛大, 小泉 誠, 大西 朗之, 高石 巨澄, 山村 智彦, 南川 将吾, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2017, 日本小児腎臓病学会雑誌, 30(2) (2), 179 - 179, Japanese

  • 三輪 沙織, 野津 寛大, 梅田 千里, 掛川 大輔, 山田 哲史, 伊藤 亮, 村上 仁彦, 南川 将吾, 飯島 一誠, 平野 大志
    (一社)日本小児腎臓病学会, Nov. 2017, 日本小児腎臓病学会雑誌, 30(2) (2), 181 - 181, Japanese

  • 三輪 沙織, 徳永 愛, 千葉 浩介, 梅田 千里, 掛川 大輔, 山田 哲史, 伊藤 亮, 村上 仁彦, 南川 将吾, 野津 寛大, 飯島 一誠, 平野 大志, 松岡 健太郎
    (一社)日本小児腎臓病学会, Nov. 2017, 日本小児腎臓病学会雑誌, 30(2) (2), 187 - 188, Japanese

  • PLCE1遺伝子変異を認めた巣状分節性糸球体硬化症の1歳児例
    今村 秀明, 此元 隆雄, 下田 貴史, 盛武 浩, 中西 啓太, 野津 寛大, 飯島 一誠, 阪口 嘉美, 久野 敏
    (一社)日本小児腎臓病学会, Nov. 2017, 日本小児腎臓病学会雑誌, 30(2) (2), 200 - 200, Japanese

  • X連鎖型女性Alport症候群の2例
    大串 栄彦, 大塚 泰史, 溝端 理恵, 陣内 久美子, 岡 政史, 佐藤 忠司, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2017, 日本小児腎臓病学会雑誌, 30(2) (2), 201 - 201, Japanese

  • 健診で偶然発見されたGitelman症候群の5歳女児例
    内村 絵美, 今村 秀明, 此元 隆雄, 布井 博幸, 野津 寛大, 久野 敏, 阪口 嘉美
    (公社)日本小児科学会, Oct. 2017, 日本小児科学会雑誌, 121(10) (10), 1739 - 1739, Japanese

  • CRB2変異によるステロイド抵抗性ネフローゼ症候群(SRNS)の1例
    渡邊 祥二郎, 相沢 知美, 津川 浩二, 敦賀 和志, 伊藤 悦朗, 田中 完, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Oct. 2017, 日本小児科学会雑誌, 121(10) (10), 1772 - 1772, Japanese

  • 遺伝子診断し得たGitelman症候群の一例
    村松 愛子, 熊谷 亮, 藤井 優尚, 片倉 幸乃, 野津 寛大, 飯島 一誠, 野牛 宏晃
    (一社)日本内分泌学会, Oct. 2017, 日本内分泌学会雑誌, 93(2) (2), 592 - 592, Japanese

  • 無症候性蛋白尿で発見された末期腎不全に移行した、INF2遺伝子変異によるFSGSの男児例
    水谷 亮, 齊藤 真人, 西野 智彦, 掛川 大輔, 櫻谷 浩志, 櫻井 俊輔, 藤永 周一郎, 野津 寛大, 中西 浩一
    日本小児PD・HD研究会, Oct. 2017, 日本小児PD・HD研究会雑誌, 29, 31 - 31, Japanese

  • NEW COMBINATION THERAPY WITH PREDNISOLONE (PSL), MIZORIBINE AND LISINOPRIL FOR SEVERE CHILDHOOD IGA NEPHROPATHY (IGAN)
    Norishige Yoshikawa, Yuko Shima, Masashi Sato, Hama Taketsugu, Hironobu Mukaiyam, Hiroko Togawa, Hiroyuki Suzuki, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Koichi Nakanishi
    SPRINGER, Sep. 2017, PEDIATRIC NEPHROLOGY, 32(9) (9), 1747 - 1747, English
    Summary international conference

  • A VARIETY OF PHENOTYPES REFLECTED BY GENOTYPES AND LAMININ beta 2 EXPRESSION ON GLOMERULUS IN PIERSON SYNDROME
    Shogo Minamikawa, Kandai Nozu, Junya Fujimura, Keita Nakanishi, Tomoko Horinouchi, Tomohiko Yamamura, Takeshi Ninchoji, Hiroshi Kaito, Norishige Yoshikawa, Kazumoto Iijima
    SPRINGER, Sep. 2017, PEDIATRIC NEPHROLOGY, 32(9) (9), 1756 - 1756, English
    Summary international conference

  • IN VITRO SPLICING ASSAYS TO DETECT INTRONIC PATHOGENIC VARIANTS IN INHERITED KIDNEY DISEASES
    Keita Nakanishi, Kandai Nozu, Junya Fujimura, Tomoko Horinouchi, Tomohiko Yamamura, Shogo Minamikawa, Takeshi Ninchoji, Hiroshi Kaito, Norishige Yoshikawa, Kazumoto Iijima
    SPRINGER, Sep. 2017, PEDIATRIC NEPHROLOGY, 32(9) (9), 1754 - 1754, English
    Summary international conference

  • 各種疾患の移行医療 現状と課題 ネフローゼ症候群と移行医療
    堀之内 智子, 野津 寛大, 飯島 一誠
    (有)科学評論社, Sep. 2017, 腎臓内科・泌尿器科, 6(3) (3), 245 - 248, Japanese

  • EYA1遺伝子欠損による鰓弓耳腎症候群の1例
    岩重 洋平, 伊東 悠貴, 嘉藤 光歩, 大棟 浩平, 杉谷 盛太, 前沢 浩司, 東 義人, 森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 723 - 723, Japanese

  • 遺伝性腎疾患における遺伝子診断の現状とこれからの課題
    野津 寛大
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 857 - 857, Japanese

  • TGFBI関連眼腎症候群の1例 顆粒状角膜ジストロフィII型と腎症の合併例
    岩渕 洋一, 森岡 哲夫, 小山 裕子, 野津 寛大, 飯島 一誠, 成田 一衛
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 871 - 871, Japanese

  • シクロスポリンの効果は一時的であったACTN4新規遺伝子変異を伴うFSGS男児例
    櫻谷 浩志, 藤永 周一郎, 中西 啓太, 野津 寛大
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 875 - 875, Japanese

  • 糖尿病合併のないA3243G変異ミトコンドリア病によるFSGSの一例
    渡邉 駿, 小黒 昌彦, 鳥生 直哉, 稲永 亮平, 井熊 大輔, 大島 洋一, 早見 典子, 住田 圭一, 山内 真之, 関根 章成, 川田 真宏, 長谷川 詠子, 星野 純一, 澤 直樹, 高市 憲明, 大橋 健一, 土谷 良樹, 野津 寛大, 乳原 善文
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 906 - 906, Japanese

  • 腎病理所見にて髄質嚢胞腎(MCKD)の特徴を認めた2例
    岡田 絵里, 川口 武彦, 森 維久郎, 山田 亜純, 上原 正樹, 岡島 真里, 山川 貴史, 首村 守俊, 北村 博司, 森貞 直哉, 野津 寛大, 今澤 俊之
    (一社)日本腎臓学会, Sep. 2017, 日本腎臓学会誌, 59(6) (6), 928 - 928, Japanese

  • 蛋白尿、高血圧を認め24時間自由行動下血圧測定を施行した極低出生体重の1例
    山村 智彦, 中西 啓太, 藤村 順也, 南川 将吾, 忍頂寺 毅史, 野津 寛大, 飯島 一誠
    症例は18歳男性。学校検尿で蛋白尿を指摘され近医を経て当科を受診した。早朝尿検査にて蛋白尿を認めた他、随時血圧高値を認めた。以後の外来受診時の血圧が138-156/71-89mmHg程度で推移したため高血圧と診断し、治療開始前の日内変動の確認のために24時間自由行動下血圧測定(ABPM)を施行した。その結果、24時間収縮期圧125mmHg、睡眠時血圧108mmHg、覚醒時血圧130mmHgと高血圧は認めず白衣高血圧と診断した。本症例は蛋白尿の他に片側の腎萎縮を有する極低出生体重児という既往歴・周産期歴を持ち高血圧のリスク群と考えられる症例であり、複数回の随時血圧測定により高血圧と診断した。しかし、治療開始直前に日内変動の把握のためにABPMを行った結果、白衣高血圧と判明した。病歴等から高血圧の存在を強く疑う患者においてもABPMによる精査が必要であることを改めて認識させられた貴重な症例であった。(著者抄録)
    日本小児高血圧研究会, Jun. 2017, 日本小児高血圧研究会誌, 14(1) (1), 32 - 36, Japanese

  • 【腎再生医療】 遺伝性腎疾患と分子生物学的治療
    野津 寛大
    (有)科学評論社, Jun. 2017, 腎臓内科・泌尿器科, 5(6) (6), 570 - 573, Japanese

  • ナットクラッカー現象を合併した起立性蛋白尿の1例
    堀之内 智子, 南川 将吾, 山村 智彦, 神吉 直宙, 忍頂寺 毅史, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, May 2017, 日本小児科学会雑誌, 121(5) (5), 903 - 903, Japanese

  • 成長障害の経過観察中に四肢麻痺をきたし診断に至った尿細管性アシドーシスの1例
    藤村 順也, 忍頂寺 毅史, 中西 啓太, 堀之内 智子, 南川 将吾, 山村 智彦, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, May 2017, 日本小児科学会雑誌, 121(5) (5), 908 - 908, Japanese

  • 24時間自由行動下血圧測定が高血圧診療に有用であった1例
    山村 智彦, 中西 啓太, 藤村 順也, 南川 将吾, 忍頂寺 毅史, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, May 2017, 日本小児科学会雑誌, 121(5) (5), 913 - 913, Japanese

  • 未診断疾患における網羅的ゲノム解析時代の遺伝カウンセリング 小児CKD(慢性腎臓病)の原因遺伝子解析と遺伝カウンセリング
    森貞 直哉, 野津 寛大, 飯島 一誠
    日本遺伝カウンセリング学会, May 2017, 日本遺伝カウンセリング学会誌, 38(2) (2), 55 - 55, Japanese

  • ゲノム情報を臨床へ 遺伝性腎疾患へのアプローチ バイオサイエンスデータベースを使った解析手法
    野津 寛大
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 63 - 63, Japanese

  • エクソンスキッピング療法によるアルポート症候群特異的治療法の開発
    庄野 朱美, 野津 寛大, 小泉 誠, 大西 朗之, 高石 巨澄, 山村 智彦, 南川 将吾, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 102 - 102, Japanese

  • 三輪 沙織, 野津 寛大, 梅田 千里, 掛川 大輔, 山田 哲史, 伊藤 亮, 村上 仁彦, 南川 将吾, 飯島 一誠, 平野 大志
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 106 - 106, Japanese

  • 藤村 順也, 忍頂寺 毅史, 中西 啓太, 堀之内 智子, 山村 智彦, 南川 将吾, 貝藤 裕史, 野津 寛大, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 153 - 153, Japanese

  • Lowe症候群およびDent2の分子生物学的検討
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 山村 智彦, 貝藤 裕史, 前川 講平, 依藤 亨, 原田 真理, 五十嵐 徹, 平本 龍吾, 田中 亮二郎, 松山 健, 長谷 幸治, 沖 栄真, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 174 - 174, Japanese

  • 先天性ネフローゼ症候群/乳児ネフローゼ症候群およびステロイド抵抗性ネフローゼ症候群における網羅的遺伝子診断体制の構築
    中西 啓太, 野津 寛大, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 忍頂寺 毅史, 貝藤 裕史, 島 友子, 中西 浩一, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 181 - 181, Japanese

  • In vivoおよびin vitroの解析によりsplicing異常による疾患発症を証明したフィブロネクチン腎症の一例
    辻 ゆり佳, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 南川 将吾, 忍頂寺 毅史, 貝藤 裕史, 祖父江 理, 原 重雄, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 186 - 186, Japanese

  • 無症候性蛋白尿を呈し次世代シークエンサーにてNPHS1遺伝子異常を同定した女児例
    山田 剛史, 長谷川 博也, 山村 智彦, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 187 - 187, Japanese

  • C1qの沈着を伴った常染色体優性Alport症候群の1例
    波多江 健, 檜山 麻衣子, 黒木 理恵, 中川 兼康, 野津 寛大, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 210 - 210, Japanese

  • Alport症候群9家系の臨床的検討
    大串 栄彦, 大塚 泰史, 溝端 理恵, 陣内 久美子, 岡 政史, 佐藤 忠司, 野津 寛大, 飯島 一誠, 松尾 宗明
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 211 - 211, Japanese

  • minigeneを用いた遺伝性腎疾患におけるpathogenic splicing variantの同定
    山村 智彦, 野津 寛大, 久富 隆太郎, 上田 博章, 藤丸 季可, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 庄野 朱美, 忍頂寺 毅史, 貝藤 裕史, 中西 浩一, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 211 - 211, Japanese

  • NGSターゲット遺伝子シークエンスパネルによるCAKUTおよびNPHの包括的原因遺伝子解析
    森貞 直哉, 庄野 朱美, 野津 寛大, 忍頂寺 毅史, 叶 明娟, 井藤 奈央子, 神田 祥一郎, 亀井 宏一, 石倉 健司, 伊藤 秀一, 山本 勝輔, 塚口 裕康, 里村 憲一, 田中 亮二郎, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2017, 日本小児腎臓病学会雑誌, 30(1Suppl.) (1Suppl.), 212 - 212, Japanese

  • 【小児科ケースカンファレンス】 腎・泌尿器疾患、生殖器疾患 Gitelman症候群
    野津 寛大
    (株)診断と治療社, Apr. 2017, 小児科診療, 80(増刊) (増刊), 334 - 337, Japanese

  • マイクロRNAによる多発性嚢胞腎疾患特異的治療の検討
    佐藤 匡, 中西 浩一, 浜 武継, 向山 弘展, 戸川 寛子, 島 友子, 宮嶋 正康, 野津 寛大, 長尾 枝澄香, 高橋 久英, 飯島 一誠, 吉川 徳茂, 鈴木 啓之
    多発性嚢胞腎(polycystic kidney disease:PKD)では嚢胞上皮細胞の極性が消失し、増殖・分泌・細胞外基質異常が起こる。PKDの病態にマイクロRNA(miRNA)の関与が報告されているが、詳細は不明である。私どもはcpkマウスでmiRNAとその関連分子を評価し、疾患特異的治療のための基礎的データを収集し、それらのバイオマーカーとしての可能性を検討した。ARPKDモデルマウスであるcpkマウスにおいて、miRNAマイクロアレイにより病態に関与すると推定されたmiRNA、miR-378a-3pを同定した。cpkマウスにおいて、対照と比較してmiR-378a-3pの発現をreal-time PCRで確認したところ、マイクロアレイの結果と同様に、cpkマウスにおいて減少を認め、日齢を経過するとそれがさらに減少していた。また尿においても同様の変化を認めており、疾患活動性を評価するバイオマーカーとしての可能性が示唆された。(著者抄録)
    発達腎研究会, Apr. 2017, 発達腎研究会誌, 25(1) (1), 34 - 36, Japanese

  • 偶然見つかったGitelman症候群の2例
    松下 詠治, 平尾 正人, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Apr. 2017, 日本小児科学会雑誌, 121(4) (4), 780 - 780, Japanese

  • Alport症候群の臨床遺伝学的研究
    野津 寛大
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 185 - 185, Japanese

  • 難治性腎疾患における新規治療標的分子 遺伝性疾患におけるエクソンスキッピング療法の現状と腎疾患への応用の可能性
    野津 寛大, 庄野 朱美, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 205 - 205, Japanese

  • NPH・MCKDの遺伝子診断と病型
    森貞 直哉, 野津 寛大, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 218 - 218, Japanese

  • 小児IgA腎症における糸球体毛細管係蹄(cap)IgA沈着の臨床病理学的検討
    島 友子, 中西 浩一, 佐藤 匡, 浜 武継, 向山 弘展, 戸川 寛子, 貝藤 裕史, 野津 寛大, 田中 亮二郎, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 251 - 251, Japanese

  • 医師主導治験でリツキシマブの投与を行った小児期発症難治性ネフローゼ症候群患者の長期予後
    亀井 宏一, 石倉 健司, 佐古 まゆみ, 綾 邦彦, 田中 亮二郎, 野津 寛大, 貝藤 裕史, 中西 浩一, 大友 義之, 三浦 健一郎, 高橋 昌里, 森本 哲司, 久保田 亘, 伊藤 秀一, 飯島 一誠, RCRNS study group
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 252 - 252, Japanese

  • 女性Dent病における遺伝学的背景
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 忍頂寺 毅史, 島 友子, 中西 浩一, 服部 益治, 神田 杏子, 田中 亮二郎, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 257 - 257, Japanese

  • 次世代シークエンサーを用いたAlport症候群の網羅的診断法の確立
    山村 智彦, 野津 寛大, 藤村 順也, 堀之内 智子, 中西 啓太, 南川 将吾, 庄野 朱美, 忍頂寺 毅史, 貝藤 裕史, 中西 浩一, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 314 - 314, Japanese

  • NGSターゲット遺伝子シークエンスパネルによるCAKUTおよびNPHの包括的原因遺伝子解析
    森貞 直哉, 庄野 朱美, 野津 寛大, 忍頂寺 毅史, 田中 亮二郎, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2017, 日本腎臓学会誌, 59(3) (3), 314 - 314, Japanese

  • 波多江 健, 慶田 裕美, 檜山 麻衣子, 黒木 理恵, 黒川 麻里, 森貞 直哉, 野津 寛大, 飯島 一誠
    PAX2の変異はCAKUTや腎コロボーマ症候群(renal coloboma syndrome:RCS)の原因となる。私達は腎低異形成の乳児で、偽性Bartter症候群を呈した症例を経験した。児は41週3,116gにて出生。4生日に11%の体重減少がありミルク追加を指示されたが哺乳瓶をいやがり母乳のみで栄養されていた。2ヵ月時、体重増加不良を指摘され当院へ紹介された。78生日、体重3,930g。血液検査で尿素窒素23.1mg/dl、Cr0.57mg/dl、超音波検査で両側に小さく高輝度の腎を認め、腎低異形成と診断した。眼科検査は異常なし。6ヵ月時、アルカローシス、低K血症を認めBartter症候群を疑った。Bartter症候群およびCAKUT関連遺伝子の解析を行い、次世代シークエンサーによる遺伝子解析にてPAX2のexon2に一塩基挿入を認めた(NM_003987.3:c.76dupG、p.Val26Glyfs*28)。再度眼底検査を行い軽度の視神経乳頭の変化を認めRCSの診断に至った。(著者抄録)
    (一社)日本小児腎臓病学会, Apr. 2017, 日本小児腎臓病学会雑誌, 30(1) (1), 54 - 59, Japanese

  • Kazumoto Iijima, Mayumi Sako, Kandai Nozu
    Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.
    SPRINGER, Apr. 2017, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 21(2) (2), 193 - 202, English
    [Refereed]
    Book review
    Link to Kobe Univ. Repository (Kernel)

  • 【腎臓医が知っておきたい分子遺伝学の進歩】 疾患編 Alport症候群
    野津 寛大
    (株)東京医学社, Mar. 2017, 腎と透析, 82(3) (3), 383 - 388, Japanese

  • 若い先生に「リサーチマインドを」 明日の小児科を築くPhysician scientistを 遺伝性腎疾患の研究から学んだ大切なこと 研究の楽しさと臨床へのフィードバック
    野津 寛大
    (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 187 - 187, Japanese

  • 下痢関連溶血性尿毒症症候群(D+HUS)の急性期経過と予後
    藤村 順也, 忍頂寺 毅史, 中西 啓太, 山村 智彦, 南川 将吾, 貝藤 裕史, 野津 寛大, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 235 - 235, Japanese

  • 小児期にCKDに至ったX染色体連鎖型Alport症候群の女児例
    塚田 瑞葉, 西野 智彦, 齊藤 真人, 掛川 大輔, 櫻谷 浩志, 櫻井 俊輔, 藤永 周一郎, 清水 俊明, 佐渡 義一, 野津 寛大
    (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 236 - 236, Japanese

  • 腎外症状を呈さないCRB2変異によるステロイド抵抗性ネフローゼ症候群(SRNS)の1例
    渡辺 祥二郎, 津川 浩二, 敦賀 和志, 伊藤 悦朗, 田中 完, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 420 - 420, Japanese

  • NCCT機能異常を伴う偽性副甲状腺機能低下症の一例
    小木曽 和磨, 郡山 暢之, 野津 寛大, 大保 崇彦, 時任 紀明, 西尾 善彦
    (一社)日本内分泌学会, Dec. 2016, 日本内分泌学会雑誌, 92(S.Branc) (S.Branc), 355 - 355, Japanese

  • 【腎生検病理診断の実際と新たな展開】 遺伝性腎疾患の最近の進歩
    山村智彦, Nozu Kandai, Iijima Kazumoto
    (株)文光堂, Dec. 2016, 病理と臨床, 34(12号) (12号), 1317 - 1325, Japanese
    [Refereed]
    Introduction scientific journal

  • 大坪 裕美, 野津 寛大, 飯島 一誠
    フィブロネクチン腎症(Fibronectin glomerulopathy)は腎糸球体内へのFNの多量の沈着を特徴とする常染色体優性遺伝性腎疾患として1995年に初めて報告された。10歳後半から30歳前後に尿所見の異常で発症し、約90%の患者に蛋白尿を認め、時にネフローゼ状態を呈することもある。約半数の患者が高血圧を合併し、約25%の患者が発症後おおむね15〜20年で末期腎不全に至り腎代替療法が必要となる。しかし、腎移植後は高率に移植後再発をきたす予後不良な疾患である。2007年に責任遺伝子(FN1)が同定されたが、病因・病態はいまだ十分に解明されていない。(著者抄録)
    (一社)日本小児腎臓病学会, Nov. 2016, 日本小児腎臓病学会雑誌, 29(2) (2), 137 - 141, Japanese

  • 山村 智彦, 野津 寛大, 中西 啓太, 堀之内 智子, 藤村 順也, 南川 将吾, 神吉 直宙, 忍頂寺 毅史, 貝藤 裕史, 森貞 直哉, 中西 浩一, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2016, 日本小児腎臓病学会雑誌, 29(2) (2), 180 - 180, Japanese

  • 女性のDent病患者2例における発症機序に関する考察
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 山村 智彦, 神吉 直宙, 忍頂寺 毅史, 島 友子, 中西 浩一, 服部 益治, 飯島 一誠
    (一社)日本小児腎臓病学会, Nov. 2016, 日本小児腎臓病学会雑誌, 29(2) (2), 182 - 182, Japanese

  • 忍頂寺毅史, 貝藤裕史, Nozu Kandai, 飯島一誠
    紫斑病性腎炎(HSPN)はHenoch-Schoenlein紫斑病(HSP)に伴う腎炎で、小児腎臓科医が診療する最も頻度の高い疾患の一つである。数%が末期腎不全に至るとされる一方で、腎炎を発症しても自然治癒する例があることも知られている。治療方針に確固たるエビデンスがないため、施設や症例ごとに治療法や治療開始のタイミングが異なるのが現状である。当院ではこれまで一貫して、血清アルブミン値と病理組織学的所見に基づき治療方針を決定し、免疫抑制剤などによる濃厚な治療の対象をできるだけ限定するよう努めてきた。その後方視的解析の結果、アンギオテンシン変換酵素阻害薬(ACE-I)あるいはアンギオテンシンII受容体拮抗薬(ARB)を使用することで、比較的重度なHSPN症例でも良好な予後であることを明らかにした。ACE-I/ARBは、その効果と限界を理解したうえであればHSPNに対しても使用が可能である。(著者抄録)
    (一社)日本小児腎臓病学会, Nov. 2016, 日本小児腎臓病学会雑誌, 29(2号) (2号), 109 - 113, Japanese
    [Refereed]
    Introduction scientific journal

  • Crescentic IgA Nephropathy in children.
    Y. Shima, K. Nakanishi, M. Sato, K. Nozu, R. Tanaka, K. Iijima, H. Suzuki, N. Yoshikawa
    SPRINGER, Oct. 2016, PEDIATRIC NEPHROLOGY, 31(10) (10), 1819 - 1819, English
    Summary international conference

  • Genetic and clinical characteristics of female X-linked Alport syndrome: 267 cases study
    T. Yamamura, K. Nozu, K. Nakanishi, S. Minamikawa, T. Ninchoji, K. Nakanishi, N. Yoshikawa, K. Iijima
    SPRINGER, Oct. 2016, PEDIATRIC NEPHROLOGY, 31(10) (10), 1751 - 1751, English
    Summary international conference

  • Clinical characteristics and long term outcome of diarrhea associated hemolytic uremic syndrome
    K. Nakanishi, T. Ninchoji, T. Yamamura, S. Minamikawa, K. Nozu, K. Nakanishi, N. Yoshikawa, K. Iijima
    SPRINGER, Oct. 2016, PEDIATRIC NEPHROLOGY, 31(10) (10), 1870 - 1870, English
    Summary international conference

  • Genetic approach to the siblings with congenital/infantile nephrotic syndrome by targeted resequencing
    S. Minamikawa, K. Nozu, K. Nakanishi, T. Yamamura, T. Ninchoji, K. Nakanishi, N. Yoshikawa, K. Iijima
    SPRINGER, Oct. 2016, PEDIATRIC NEPHROLOGY, 31(10) (10), 1831 - 1832, English
    Summary international conference

  • 【慢性疾患児の一生を診る】 腎尿路疾患 Bartter症候群・Gitelman症候群
    貝藤裕史, Nozu Kandai
    (株)東京医学社, Oct. 2016, 小児内科, 48(10号) (10号), 1618 - 1620, Japanese
    [Refereed][Invited]
    Introduction scientific journal

  • 遺伝子解析により早期診断に至ったGitelman症候群の2例
    菅谷 憲太, 只木 弘美, 伊奈 真一郎, 福冨 崇浩, 村田 宗紀, 和田 芳雅, 早野 聡子, 植田 晶子, 粟生 耕太, 友野 順章, 野津 寛大, 飯島 一誠, 伊藤 秀一
    Gitelman症候群(GS)はNa-Cl共輸送体をコードする遺伝子SLC12A3に異常を呈する常染色体劣性遺伝性疾患であり、確定診断には遺伝子解析が必要となる。【症例1】1歳4ヵ月女児。無熱性痙攣のために当院に救急搬送となった。低K血症、代謝性アルカローシスなどの検査値からGSを疑い遺伝子解析を行った結果、SLC12A3に複合ヘテロ接合体遺伝子変異が認められGSと診断した。【症例2】5歳男児。発熱のために当院受診。低K血症などの検査値からGSを疑い遺伝子解析を行った結果、SLC12A3に新規のミスセンス変異を含む複合ヘテロ接合体遺伝子変異が認められGSと診断した。本症例は2例ともに低年齢での発症で平常時には検査値の異常を認めていない。電解質補正が必要となることもあるため、GSが疑われる症例では遺伝子解析による早期診断が重要である。(著者抄録)
    日本小児腎不全学会, Jul. 2016, 日本小児腎不全学会雑誌, 36, 331 - 334, Japanese

  • 佐藤 匡, 中西 浩一, 浜 武継, 向山 弘展, 戸川 寛子, 島 友子, 宮嶋 正康, 野津 寛大, 長尾 枝澄香, 高橋 久英, 飯島 一誠, 吉川 徳茂, 鈴木 啓之
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 174 - 174, Japanese

  • 平滑筋腫を合併したアルポート症候群の臨床像と遺伝学的検討
    南川 将吾, 野津 寛大, 中西 啓太, 藤村 順也, 堀之内 智子, 神吉 直宙, 忍頂寺 毅史, 長野 智那, 後藤 芳充, 平野 大志, 藤永 周一郎, 高橋 英彦, 森下 高弘, 森貞 直哉, 田村 雅仁, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2016, 日本小児腎臓病学会雑誌, 29(1Suppl.) (1Suppl.), 95 - 95, Japanese

  • 【腎と透析診療指針2016】 (第8章)その他の糸球体疾患 Alport症候群
    神吉直宙, Nozu Kandai, Iijima Kazumoto
    Jun. 2016, 腎と透析, 80(増刊) (増刊), 272 - 276, Japanese
    [Refereed]
    Introduction scientific journal

  • 次世代シークエンサーを用いた先天性腎尿路奇形(CAKUT)の原因遺伝子解析
    森貞直哉, 庄野朱美, Nozu Kandai, 叶明娟, 神田祥一郎, 井藤奈央子, 亀井宏一, 伊藤秀一, 山本勝輔, 里村憲一, 田中亮二郎, Nishio Hisahide, Iijima Kazumoto
    先天性腎尿路奇形(congenital anomalies of the kidney and urinary tract、CAKUT)はさまざまな腎尿路の形態異常の総称である。一部のCAKUTにはその原因に遺伝子の異常が関与していると言われ、これまでに多くのCAKUT原因遺伝子が報告されている。しかしCAKUTは表現型が類似しているため臨床症状から特定の原因遺伝子を推測することが難しいことから、原因遺伝子の包括的な遺伝子解析が必要と考えている。われわれは臨床的に原因遺伝子の推定が困難なCAKUTおよび小児期発症の原因不明腎機能障害患者44例に対し、CAKUTおよびCAKUTと臨床的に鑑別が困難なネフロン癆、遺伝性巣状糸球体硬化症の原因遺伝子91種類を網羅した遺伝子解析パネルを作成し、次世代シークエンサー(next generation sequencing、NGS)によるターゲットリシークエンスを施行した。その結果約18%の症例で遺伝子変異を同定した。NGSによる遺伝子解析は近年さまざまな臨床の現場で急速に広まっており、遺伝性小児腎疾患の分野でも診断の確定と治療方針の策定に有用な方法であると考えられた。(著者抄録)
    発達腎研究会, Apr. 2016, 発達腎研究会誌, 24(1) (1), 13 - 15, Japanese
    [Refereed]
    Introduction scientific journal

  • 【小児の症候群】 腎・泌尿器 Gitelman症候群
    Nozu Kandai
    Apr. 2016, 小児科診療, 79(増刊) (増刊), 300, Japanese
    [Refereed]
    Introduction scientific journal

  • 【小児の症候群】 腎・泌尿器 Bartter症候群
    Nozu Kandai
    Apr. 2016, 小児科診療, 79(増刊) (増刊), 294, Japanese
    [Refereed][Invited]
    Introduction scientific journal

  • 常染色体劣性型か常染色体優性型かの判別に苦慮したAlport症候群の一女児例
    藤井裕子, 藤井裕子, 芦田明, 松村英樹, 白数明彦, 山崎哲司, 中倉兵庫, 野津寛大, 飯島一誠, 玉井浩
    2016, 日本小児腎不全学会学術集会プログラム・抄録集, 38th

  • 腰部脊柱管狭窄症により顕性化し、負荷試験と遺伝子検査で確定診断できた高齢者Gitelman症候群の1例
    井上 光子, 林 哲載, 桃園 明, 鎌田 裕二, 高野 幸路, 野津 寛大, 飯島 一誠, 七里 眞義
    (一社)日本内分泌学会, Dec. 2015, 日本内分泌学会雑誌, 91(Suppl.Branch) (Suppl.Branch), 119 - 119, Japanese

  • GENETIC, PATHOLOGICAL AND CLINICAL BACKGROUNDS IN AUTOSOMAL DOMINANT ALPORT SYNDROME
    Kandai Nozu, Naohiro Kamiyoshi, Natsuki Matsunoshita, Shogo Minamikawa, Tomohiko Yamamura, Takeshi Ninchoji, Ryojiro Tanaka, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima
    SPRINGER, Sep. 2015, PEDIATRIC NEPHROLOGY, 30(9) (9), 1669 - 1669, English
    Summary international conference

  • Branchio-oto-renal(BOR)症候群の原因遺伝子と腎症状に関する検討
    森貞 直哉, 野津 寛大, 松永 達雄, 飯島 一誠
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 152 - 152, Japanese

  • cpkマウスにおける嚢胞形成に対するsmad3ノックアウトの効果
    佐藤 匡, 中西 浩一, 浜 武継, 向山 弘展, 戸川 寛子, 島 友子, 宮嶋 正康, 野津 寛大, 長尾 枝澄香, 高橋 久英, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 90 - 90, Japanese

  • 【内科疾患の診断基準・病型分類・重症度】(第3章)腎臓 診断メモ 先天性ネフローゼ/乳児ネフローゼ症候群
    野津寛大, Iijima Kazumoto
    Jun. 2015, 内科, 115(6号) (6号), 1036, Japanese
    Introduction scientific journal

  • 【内科疾患の診断基準・病型分類・重症度】(第3章)腎臓 診断メモ Bartter症候群・Gitelman症候群 遺伝性塩類喪失性尿細管機能異常症
    野津寛大, Iijima Kazumoto
    Jun. 2015, 内科, 115(6号) (6号), 1039, Japanese
    Introduction scientific journal

  • 【内科疾患の診断基準・病型分類・重症度】(第3章)腎臓 診断メモ Alport症候群
    野津寛大, Iijima Kazumoto
    Jun. 2015, 内科, 115(6号) (6号), 1037, Japanese
    Introduction scientific journal

  • RAAS blockの開始時期により腎機能の経過が異なった常染色体劣性Alport症候群の3姉弟例
    内田 奈生, 熊谷 直憲, 付 学軍, 野津 寛大, 飯島 一誠, 根東 義明, 呉 繁夫
    (一社)日本小児腎臓病学会, Jun. 2015, 日本小児腎臓病学会雑誌, 28(1Suppl.) (1Suppl.), 124 - 124, Japanese

  • Branchio-oto-renal(BOR)症候群の原因遺伝子と腎症状に関する検討
    森貞 直哉, 野津 寛大, 松永 達雄, 飯島 一誠
    (一社)日本腎臓学会, Apr. 2015, 日本腎臓学会誌, 57(3) (3), 458 - 458, Japanese

  • cpkマウスにおける嚢胞形成に対するsmad3ノックアウトの効果
    浜 武継, 中西 浩一, 佐藤 匡, 向山 弘展, 戸川 寛子, 島 友子, 宮嶋 正康, 野津 寛大, 高橋 久英, 長尾 枝澄香, 飯島 一誠, 吉川 徳茂
    多発性嚢胞腎では嚢胞上皮細胞の極性の消失が認められ、増殖・分泌・細胞外器質異常が起こり、最終的に線維化が進行し腎不全に至る。嚢胞の形成機序は不明であるが、嚢胞上皮における上皮間葉移行やTGF-β/Smad3系の関与が示唆されている。Smad3のリン酸化部位には、リンカー部(Linker region:L)とC末端部(COOH terminal:C)があり、pSmad3L、pSmad3C及びpSmad3L/Cのフォスフォアイソフォームが形成されるが、このうちpSmad3L/CがJNK/CDK4を介してc-Mycを発現させていることを私たちは報告してきた。pSmad3L/Cが多発性嚢胞腎の病態に関与している可能性があり、今回、cpkマウス常染色体劣性多発性嚢胞腎モデルにおけるsmad3ノックアウトによる表現型の変化、及び、関連分子を検討した。smad3ノックアウトの結果、(1)腎体重比は有意に低下、(2)核内pJNK、pCDK4、c-Mycは有意に低下、(3)尿細管上皮におけるKi-67陽性細胞は有意に減少、(4)線維化は有意に減少した。smad3ノックアウトにより、pSmad3L/C-JNK-CDK4-c-Myc経路が抑制され、嚢胞上皮細胞の増殖が抑制された。また、TGF-β/Smad3経路も抑制され、間質の線維化が抑制された。smad3の修飾がPKDの疾患特異的治療につながる可能性が示唆された。(著者抄録)
    発達腎研究会, Apr. 2015, 発達腎研究会誌, 23(1) (1), 15 - 18, Japanese

  • 【病態生理と症例から学ぶ輸液ガイド】 (第2章)身につけておきたい水・電解質輸液の基本手技 経口補水療法の行いかた
    野津寛大, Iijima Kazumoto
    Apr. 2015, Medical Practice, 32(臨増) (臨増), 114 - 116, Japanese
    Introduction scientific journal

  • ヒトCAKUTの原因遺伝子解析
    Morisada Naoya, 野津寛大, 亀井宏一, 伊藤秀一, 田中亮二郎, Iijima Kazumoto
    先天性腎尿路奇形(CAKUT)はあらゆる腎尿路奇形の総称で、その原因の一部には遺伝子の異常が関与していると言われている。これまで多数のCAKUT原因遺伝子が報告されているが、これまでの手法ではそれらをすべて解析することは極めて困難であった。また原因遺伝子が不明の症例も多く、まだ未発見のCAKUT原因遺伝子が多数存在すると予想される。本稿では最近のゲノム解析技術の進歩を紹介し、CAKUTと遺伝子の異常について考えてみたい。(著者抄録)
    発達腎研究会, Apr. 2015, 発達腎研究会誌, 23(1) (1), 19 - 22, Japanese
    Introduction scientific journal

  • 妊娠中の低カリウム性筋症出現を契機に診断されたGitelman症候群の1例
    登丸 琢也, 堀口 和彦, 松本 俊一, 中島 康代, 石井 角保, 小澤 厚志, 渋沢 信行, 松野下 夏樹, 野津 寛大, 佐藤 哲郎, 山田 正信
    (一社)日本内分泌学会, Apr. 2015, 日本内分泌学会雑誌, 91(1) (1), 296 - 296, Japanese

  • 甲状腺中毒性周期性四肢麻痺を契機にGitelman症候群と診断された一例
    大庭 健史, 小林 俊介, 長尾 元嗣, 山本 雅昭, 松野下 夏樹, 野津 寛大, 杉原 仁
    (一社)日本内分泌学会, Apr. 2015, 日本内分泌学会雑誌, 91(1) (1), 332 - 332, Japanese

  • トピラマート開始後著明な尿細管性アシドーシスと低身長の増悪を認めた1例
    南川将吾, 神吉直宙, 松野下夏樹, 李知子, 大坪裕美, 忍頂寺毅史, 貝藤裕史, 野津寛大, 八木麻理子, 竹島泰弘, 飯島一誠
    (公社)日本小児科学会, 01 Mar. 2015, 日本小児科学会雑誌, 119(3) (3), 635 - 635, Japanese

  • Basic nephrology 分子生物学 Alport症候群の軽症亜型
    野津寛大, Iijima Kazumoto
    Jan. 2015, Annual Review腎臓, 2015, 75 - 79, Japanese
    Introduction scientific journal

  • Differential diagnosis of Bartter/Gitelman syndrome and pseudo-disorder based on clinical characteristics
    N. Matsunoshita, K. Nozu, N. Kamiyosh, K. Nakanishi, N. Yoshikawa, K. Iijima
    SPRINGER, Dec. 2014, PEDIATRIC NEPHROLOGY, 29(12) (12), 2443 - 2443, English
    Summary international conference

  • X-linked Alport syndrome patients caused by atypical splicing mutations in COL4A5
    Kandai Nozu, Naoya Morisada, Hiroshi Kaito, Takeshi Ninchoji, Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima
    SPRINGER, Sep. 2014, PEDIATRIC NEPHROLOGY, 29(9) (9), 1683 - 1683, English
    Summary international conference

  • The comprehensive genetic analysis of CAKUT in Japan
    Naoya Morisada, Kandai Nozu, Akemi Shono, Takeshi Ninchoji, Hiroshi Kaito, Koichi Kamei, Shuichi Ito, Ryojiro Tanaka, Kazumoto Iijima
    SPRINGER, Sep. 2014, PEDIATRIC NEPHROLOGY, 29(9) (9), 1684 - 1685, English
    Summary international conference

  • 【腎のたまり病】 アミロイド以外の蛋白由来物質が蓄積する疾患 フィブロネクチン関連腎症の診断と治療
    大坪 裕美, Nozu Kandai, Iijima Kazumoto
    Aug. 2014, 腎と透析, 77(2号) (2号), 207 - 209, Japanese
    [Refereed]
    Introduction commerce magazine

  • 【わかる輸液-体液の生理を知り、正しい輸液オーダーができる!-】 基礎知識編 維持輸液の役割
    Nozu Kandai
    Jul. 2014, 小児科学レクチャー, 4(3号) (3号), 539 - 547, Japanese
    Introduction scientific journal

  • 【日常診療で遭遇する小児腎泌尿器疾患とトピックス】 尿細管疾患・嚢胞性腎疾患 Bartter症候群・Gitelman症候群の診断アプローチおよび偽性Bartter症候群・偽性Gitelman症候群の診断のポイント
    Nozu Kandai, Kaito Hiroshi
    診断と治療社, Jun. 2014, 小児科診療, 77(6号) (6号), 743 - 748, Japanese
    [Refereed]
    Introduction commerce magazine

  • 【内科疾患 最新の治療 明日への指針】(第3章)腎臓 Alport症候群
    Nozu Kandai, Iijima Kazumoto
    Jun. 2014, 内科, 113(6号) (6号), 1172 - 1173, Japanese
    [Refereed]
    Introduction commerce magazine

  • マイコプラズマ肺炎を契機に診断されたGitelman症候群の1例
    二瓶 真人, 熊谷 直憲, 加賀 元宗, 中山 真紀子, 菅野 潤子, 呉 繁夫, 柿坂 庸介, 野津 寛大, 飯島 一誠
    (公社)日本小児科学会, May 2014, 日本小児科学会雑誌, 118(5) (5), 876 - 876, Japanese

  • cpkマウスにおける病的Smad3リン酸化
    浜 武継, 中西 浩一, 向山 弘展, 戸川 寛子, 佐藤 匡, 島 友子, 宮嶋 正康, 野津 寛大, 高橋 久英, 長尾 枝澄香, 飯島 一誠, 吉川 徳茂
    多発性嚢胞腎では嚢胞性上皮細胞の極性の消失が認められ、増殖・分泌・細胞外器質異常が引き起こされ、最終的に線維化が進行し腎不全に至る。その嚢胞形成の特異的なメカニズムは解明されていない。嚢胞性上皮における上皮間葉移行やTGF-β/Smad 3系の関与が示唆されているが、詳細は不明である。Smad 3のリン酸化部位には、リンカー部(L)とC末端部(C)があり、pSmad3L、pSmad3Cと、両方リン酸化されたpSmad3L/Cのフォスフォアイソフォームが形成される。しかし、PKDにおけるSmad3リン酸化の詳細は不明であり、我々はcpkマウスを用いてpSmad3L、pSmad3C、pSmad3L/Cの発現、及びその関連分子を検討した。その結果、pSmad3Lの発現がcpkマウスの尿細管上皮の核で有意に増強している一方、pSmad3Cはcpkマウスと対照に同程度発現していた。Western Blottingでは、pSmad3L、pJNK、pCDK4とc-Mycがcpkマウスの核で有意に上昇していた。TGF-βとpSmad3Cはcpkマウスと対照に同程度発現していた。免疫沈降でcpkマウスにおけるpSmad3L/Cの有意な上昇を確認した。cpkマウスにおいてTGF-β/Smad 3系は量的異常より質的異常を示し、JNK/CDK4を介した核内pSmad3L/C作用によるc-Mycの発現増強が示唆された。(著者抄録)
    発達腎研究会, Apr. 2014, 発達腎研究会誌, 22(1) (1), 15 - 17, Japanese

  • 浜 武継, 中西 浩一, 向山 弘展, 戸川 寛子, 佐藤 匡, 島 友子, 宮嶋 正康, 野津 寛大, 高橋 久英, 長尾 枝澄香, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Apr. 2014, 日本小児腎臓病学会雑誌, 27(1Suppl.) (1Suppl.), 127 - 127, Japanese

  • 【小児の治療指針】 腎・尿路 Alport症候群
    Nozu Kandai
    Apr. 2014, 小児科診療, 77(増刊) (増刊), 754 - 756, Japanese
    [Refereed]
    Introduction commerce magazine

  • 【クローズアップ 症例でみる水電解質異常】 低マグネシウム血症 遺伝性低マグネシウム血症
    Nozu Kandai
    Sep. 2013, 小児内科, 45(9号) (9号), 1704 - 1708, Japanese
    Introduction commerce magazine

  • 【クローズアップ 症例でみる水電解質異常】 低カリウム血症 Bartter症候群、Gitelman症候群
    Kaito Hiroshi, Nozu Kandai, 飯島 一誠
    Sep. 2013, 小児内科, 45(9号) (9号), 1612 - 1616, Japanese
    Introduction commerce magazine

  • 【尿細管トランスポーターの機能制御と疾患治療-トピックス】 Bartter症候群・Gitelman症候群 遺伝性塩類喪失性尿細管機能異常症(salt-losing tubulopathy)
    Nozu Kandai
    Jul. 2013, 腎と骨代謝, 26(3号) (3号), 237 - 244, Japanese
    [Refereed]
    Introduction commerce magazine

  • 【クローズアップ 負荷試験の実際2013】 腎機能検査 フロセミド負荷試験(尿酸性化能)
    Nozu Kandai
    May 2013, 小児内科, 45(5号) (5号), 940 - 941, Japanese
    Introduction commerce magazine

  • 松野下 夏樹, 貝藤 裕史, 石森 真吾, 忍頂寺 毅史, Nozu Kandai, 吉川 徳茂, 飯島 一誠
    (一社)日本小児腎臓病学会, May 2013, 日本小児腎臓病学会雑誌, 26(1Suppl.) (1Suppl.), 196 - 196, Japanese
    Introduction commerce magazine

  • 【腎疾患治療薬マニュアル2013-14】 腎疾患に対する薬剤の使用方法 Bartter症候群、Gitelman症候群
    Kaito Hiroshi, Nozu Kandai, 飯島 一誠
    Apr. 2013, 腎と透析, 74(増刊) (増刊), 280 - 282, Japanese
    Introduction commerce magazine

  • Clinical nephrology 尿細管・間質障害 先天性尿細管チャネル・輸送体異常の新たな分子機構
    Nozu Kandai
    Jan. 2013, Annual Review腎臓, 2013, 193 - 203, Japanese
    Introduction commerce magazine

  • 【腎臓症候群(第2版)上-その他の腎臓疾患を含めて-】 尿細管輸送異常症 Bartter症候群・Gitelman症候群(遺伝性塩類喪失性尿細管機能異常症)
    Nozu Kandai
    Jan. 2012, 日本臨床, (別冊腎臓症候群(上)) (別冊腎臓症候群(上)), 773 - 779, Japanese
    Introduction commerce magazine

  • 低カリウム(K)血性横紋筋融解症をきたしたGitelman症候群(GS)の女子
    熊谷 秀規, 松本 静子, 野津 寛大
    (公社)日本小児科学会, Oct. 2011, 日本小児科学会雑誌, 115(10) (10), 1596 - 1596, Japanese

  • A family with benign familial hematuria of X-linked dominant inheritance
    S. Tanaka, M. Hasui, K. Nozu, K. Iijima, K. Sugimoto, T. Takemura, K. Kaneko
    SPRINGER, May 2011, PEDIATRIC NEPHROLOGY, 26(5) (5), 827 - 827, English
    Summary international conference

  • Clinical and immunohistochemical analyses of Japanese families with autosomal alport syndrome
    M. Oka, K. Nozu, T. Ninchoji, Y. Hashimura, H. Kaito, K. Iijima, M. Matsuo
    SPRINGER, May 2011, PEDIATRIC NEPHROLOGY, 26(5) (5), 828 - 828, English
    Summary international conference

  • 検尿異常を契機に発見された腎盂内結石を伴う腎性低尿酸血症の1女児例
    西崎 直人, 平野 大志, 金井 宏明, 藤永 周一郎, 大友 義之, 清水 俊明, 賀屋 仁, 野津 寛大, 金子 一成
    (公社)日本小児科学会, Mar. 2011, 日本小児科学会雑誌, 115(3) (3), 665 - 665, Japanese

  • A MALE X-LINKED ALPORT SYNDROME WITH A DELETION OF COL4A5 GENE, EXPRESSING NORMAL PATTERN OF TYPE IV COLLAGEN ALPHA 5 CHAINS IN GBM
    E. Sawanobori, A. Umino, H. Kanai, K. Matsushita, K. Sugita, K. Higashida, K. Nozu, R. P. Krol, K. Iijima
    SPRINGER, Dec. 2010, PEDIATRIC NEPHROLOGY, 25(12) (12), 2556 - 2556, English
    Summary international conference

  • 当科におけるアルポート症候群の臨床病理学的検討
    松村 千恵子, 倉山 英昭, 伊藤 秀和, 安齋 未知子, 金本 勝義, 今澤 俊之, 北村 博司, 野津 寛大, 松永 達雄
    国立病院総合医学会, Nov. 2010, 国立病院総合医学会講演抄録集, 64回, 368 - 368, Japanese

  • Clinical Characteristics of Genetically-Proven Gitelman's Syndrome
    H. Kaito, K. Nozu, Y. Hashimura, M. Oka, T. Ninchoji, K. Nakanishi, N. Yoshikawa, K. Iijima, M. Matsuo
    SPRINGER, Sep. 2010, PEDIATRIC NEPHROLOGY, 25(9) (9), 1824 - 1824, English
    Summary international conference

  • Treatment Strategy and Outcome for Henoch-Schonlein Purpura Nephritis
    T. Ninchoji, Y. Hashimura, H. Kaito, K. Nozu, K. Kanda, I. Kamioka, Y. Shima, K. Hamahira, K. Nakanishi, R. Tanaka, K. Iijima, N. Yoshikawa, M. Matsuo
    SPRINGER, Sep. 2010, PEDIATRIC NEPHROLOGY, 25(9) (9), 1879 - 1879, English
    Summary international conference

  • Natural Remission Rate and Prognostic Factors in Childhood IgA Nephropathy with Minimal Change or Focal Mesangial Proliferation
    Y. Shima, K. Nakanishi, H. Togawa, K. Nozu, R. Tanaka, K. Iijima, N. Yoshikawa
    SPRINGER, Sep. 2010, PEDIATRIC NEPHROLOGY, 25(9) (9), 1796 - 1796, English
    Summary international conference

  • 運動後急性腎不全とPRES (Posterior reversible encephalopathy syndrome) の合併を反復した腎性低尿酸血症の1例
    島 友子, 中西 浩一, 戸川 寛子, 野津 寛大, 飯島 一誠, 吉川 徳茂
    31 Aug. 2010, 日本小児腎不全学会雑誌 : 小児腎不全研究会記事, 30, 145 - 146, Japanese

  • 腎移植後の巣状分節性糸球体硬化症 (FSGS) 再発
    野津 寛大
    31 Aug. 2010, 日本小児腎不全学会雑誌 : 小児腎不全研究会記事, 30, 32 - 33, Japanese

  • 集学的治療により救命しえたPotter sequenceの1例
    忍頂寺 毅史, 藤岡 一路, 橋村 裕也, 貝藤 裕史, 森岡 一朗, 野津 寛大, 横山 直樹, 飯島 一誠, 松尾 雅文
    羊水過少、子宮内発育遅延、前置胎盤の0歳男児症例について検討した。妊娠27週時、胎児MRIでは両側腎が認められず、Potter sequenceが疑われた。妊娠37週5日に予定帝王切開で出生した。出生後、一酸化炭素(NO)吸入療法を開始し、鎮静、循環補助のための薬剤を投与した。無尿に対しては腹膜透析(PD)を行った。その結果、血清クレアチニンは低下し、体重も適正化し、生後約3ヵ月で退院した。患者にはc.76 ins Gヘテロ接合体変異がみられた。羊水過少を伴った腎低・異型性の予後は不良であるが、生直後からの積極的な呼吸循環管理およびPD療法の活用が、予後の改善に繋がる可能性が示唆された。
    日本小児腎不全学会, Aug. 2010, 日本小児腎不全学会雑誌, 30(0) (0), 178 - 180, Japanese

  • 多くの困難を抱えた小児腎移植の検討 FSGSの二次生体腎移植 症例提示
    近本 裕子, 黒田 奈緒, 秋岡 祐子, 石田 英樹, 田邉 一成, 世川 修, 野村 実, 桑鶴 良平, 馬場園 哲也, 内田 啓子, 杉谷 篤, 野津 寛大, 服部 元史
    日本小児腎不全学会, Aug. 2010, 日本小児腎不全学会雑誌, 30, 29 - 31, Japanese

  • 戸川 寛子, 中西 浩一, 島 友子, 佐古 まゆみ, 宮嶋 正康, 野津 寛大, 飯島 一誠, 吉原 大輔, 長尾 枝澄香, 吉川 徳茂
    多発性嚢胞腎(PKD)の病態生理に関して、細胞極性の消失および上皮細胞が間葉系細胞に形態変化する現象である上皮間葉移行(EMT)の観点から最近の知見を紹介した。自然発症PKDモデルのPCKラット嚢胞性上皮細胞は嚢胞の増大に伴い間葉系の形質を獲得していた。また、E-カドヘリンの転写抑制遺伝子であるSnail1の発現亢進が認められた。しかし、PKDの進行にEMTがどのように関与しているかは不明である。
    発達腎研究会, Jul. 2010, 発達腎研究会誌, 18(1) (1), 10 - 13, Japanese

  • 低カリウム(K)血性横紋筋融解症をきたしたGitelman症候群(GS)の女子
    熊谷 秀規, 松本 静子, 野津 寛大
    (公社)日本小児科学会, Jul. 2010, 日本小児科学会雑誌, 114(7) (7), 1096 - 1096, Japanese

  • 戸川 寛子, 中西 浩一, 島 友子, 佐古 まゆみ, 向山 弘展, 宮嶋 正康, 野津 寛大, 吉原 大輔, 長尾 枝澄香, 飯島 一誠, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2010, 日本小児腎臓病学会雑誌, 23(1Suppl.) (1Suppl.), 135 - 135, Japanese

  • ヒトARPKDと相同遺伝子変異を有するPCK ratにおける上皮間葉移行
    戸川 寛子, 中西 浩一, 島 友子, 佐古 まゆみ, 向山 弘展, 宮嶋 正康, 野津 寛大, 吉原 大輔, 長尾 枝澄香, 飯島 一誠, 吉川 徳茂
    (一社)日本腎臓学会, May 2010, 日本腎臓学会誌, 52(3) (3), 383 - 383, Japanese

  • 平滑筋腫合併アルポート症候群(DL-AS)の遺伝学的検討
    岡 政史, 野津 寛大, 森貞 直哉, 平野 大志, 藤永 周一郎, 忍頂寺 毅史, 橋村 裕也, 貝藤 裕史, 飯島 一誠, 松尾 雅文
    (一社)日本腎臓学会, May 2010, 日本腎臓学会誌, 52(3) (3), 302 - 302, Japanese

  • Kandai Nozu
    Apr. 2010, Pediatric Research, 67(4) (4), 444 - 445, English
    Report scientific journal

  • Gitelman症候群の小児にみられた低カリウム血性横紋筋融解症
    熊谷 秀規, 松本 静子, 野津 寛大
    (公社)日本小児科学会, Feb. 2010, 日本小児科学会雑誌, 114(2) (2), 230 - 230, Japanese

  • 腎性低尿酸血症における運動後急性腎不全の病因に関する検討 : 運動負荷時の酸化ストレス度と抗酸化力の不均衡
    武輪 鈴子, 谷口 奈穂, 田邉 裕子, 田中 幸代, 中野 崇秀, 磯崎 夕佳, 蓮井 正史, 金子 一成, 野津 寛大
    15 Nov. 2009, 日本小児腎臓病学会雑誌 = Japanese journal of pediatric nephrology, 22(2) (2), 219 - 219, Japanese

  • Renal condition in IPEX Syndrome
    HASHIMURA Yuya, NOZU Kandai, KANDA Kyoko, HAYAKAWA Akira, TAKESIMA Yasuhiro, KANEGANE Hirokazu, MIYAWAKI Toshio, IIJIMA Kazumoto, MATSUO Masafumi
    &nbsp;Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutations in the <i>FOXP3</i> gene that result in the defective development of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells. In the absence of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells, activated CD4<sup>+</sup> T cells instigate multi-organ damage. IPEX syndrome is often initially treated with immunosuppressive drugs, but only allogeneic hematopoietic stem cell transplantation has offered the possibility of cure. Kidney complications in IPEX syndrome patients have been reported to be membranous nephropathy, tubulointerstitial damage and minimal change nephritic syndrome (MCNS). We suspected that this complication is caused by a disorder of a T cell function due to IPEX syndrome. Now we report the relationship between IPEX syndrome and its complication of the kidney disease from a point of view of regulatory T cells.
    The Japanese Society for Pediatric Nephrology, 15 Nov. 2009, Nihon Shoni Jinzobyo Gakkai Zasshi, 22(2) (2), 131 - 135, Japanese

  • 1998〜2005年末までの期間に発生した15歳未満の末期腎不全症例の2007年末の状態に関する追跡調査 集計結果の報告
    服部 元史, 松永 明, 五十嵐 徹, 伊丹 儀友, 伊藤 秀一, 上村 治, 大田 敏之, 桑門 克治, 佐々木 聡, 里村 憲一, 野津 寛大, 波多江 健, 幡谷 浩史, 平松 美佐子, 和田 尚弘, 日本小児腎臓病学会統計調査委員会
    1998年1月〜2005年12月に新規登録された15歳未満の小児末期腎不全469例(男児267例、女児202例)を対象に、2007年末の状態に関する追跡調査を行った。追跡対象症例の回収率は98.7%で、0〜4歳177例(男児105例、女児72例)、5〜9歳83例(男児48例、女児35例)、10〜14歳209例(男児114例、女児95例)であった。治療は腹膜透析導入376例(80.2%)、先行的腎移植45例(9.6%)、血液透析導入43例(9.6%)、透析導入せず死亡5例(1.0%)であった。死亡5例の原因疾患は先天性ネフローゼ2例、染色体異常1例、コッケイン症候群1例、両側低・異形成腎1例であった。5例を除いた464例中、317例(68.3%)で合計322回の腎移植が実施されうち41回(12.7%)は献腎移植であった。464例の死亡症例は50例で死亡時の腎代替法は腹膜透析45例、血液透析3例、腎移植2例であった。
    (一社)日本小児腎臓病学会, Nov. 2009, 日本小児腎臓病学会雑誌, 22(2) (2), 226 - 228, Japanese
    Others

  • 運動後急性腎不全 (ALPE) を呈しPRES (Posterior Reversible Encephalopathy Syndrome) を合併した腎性低尿酸血症の1例
    島 友子, 中西 浩一, 渋田 昌一, 戸川 寛子, 尾鼻 美奈, 野津 寛大, 貝藤 裕史, 飯島 一誠, 吉川 徳茂
    31 Aug. 2009, 日本小児腎不全学会雑誌 : 小児腎不全研究会記事, 29, 120 - 121, Japanese

  • 当院にて2007年以降に経験した小児献腎移植の4例
    兵頭 洋二, 石村 武志, 竹田 雅, 貝藤 裕史, 神田 杏子, 野津 寛大, 三宅 秀明, 田中 一志, 武中 篤, 飯島 一誠, 藤澤 正人
    31 Aug. 2009, 日本小児腎不全学会雑誌 : 小児腎不全研究会記事, 29, 198 - 200, Japanese

  • 多重リスクに対し検討を重ね二次生体腎移植に成功した巣状分節性糸球体硬化症の1小児例
    黒田 奈緒, 近本 裕子, 松村 英樹, 藤木 拓磨, 藤井 寛, 久野 正貴, 秋岡 祐子, 石田 英樹, 田邉 一成, 世川 修, 車 有紀, 椎名 恭子, 野村 実, 桑鶴 良平, 馬場園 哲也, 内田 啓子, 星井 恵英里, 岡部 祥, 坂本 倫美, 杉谷 篤, 貝藤 裕史, 野津 寛大, 服部 元史
    7歳9ヵ月女児。二次生体腎移植の目的で入院した。前回は2歳6ヵ月時に母をドナーとして右腸骨窩生体腎移植術および両側自己腎摘出術を施行したが、巣状分節性糸球体硬化症(FSGS)の再発、シクロスポリンの急性毒症のため移植腎を摘出していた。患児はバスキュラーアクセスの留置を繰り返したため主要血管は閉塞・狭窄し、左上肢内のシャントのため特異な血行路を形成していた。さらに前回と同じ場所へ腎移植を予定したため癒着剥離に伴う術中大量出血の危険性があり、術前に透視下で上大静脈を確保した。また、抗HLA抗体を多数検出したため、術前にリツキシマブ投与、ガンマグロブリン大量療法および全血漿交換法を実施して腎移植を施行した。移植後血清クレアチニン値が上昇したため移植腎生検を施行し、タクロリスムの急性毒症が疑われたため投与量を減量したが、1年経過してFSGSの再発はなく、移植腎機能も良好に推移している。
    日本小児腎不全学会, Aug. 2009, 日本小児腎不全学会雑誌, 29, 179 - 182, Japanese

  • 急性膵炎を契機に発見されたGitelman症候群の1例
    森下高弘, 丸谷隆光, 後藤元秀, 佐藤弘, 神代万壽美, 森貞直哉, 荒木俊介, 白幡聡, 野津寛大
    01 Jul. 2009, 日本小児科学会雑誌, 113(7) (7), 1177 - 1178, Japanese

  • Alport症候群 (特集 小児疾患における臨床遺伝学の進歩) -- (話題の疾患遺伝子)
    野津 寛大, 飯島 一誠, 松尾 雅文
    金原出版, Jun. 2009, 小児科, 50(7) (7), 1017 - 1021, Japanese

  • 遺伝性腎疾患におけるintron内の変異に伴う病気発症メカニズム解明のためのin vivoおよびin vitroの実験系の確立
    野津寛大, 野津圭美, 齋木加代子, 西田篤丈, 貝藤裕史, 神田杏子, 橋村裕也, 中西浩一, 吉川徳茂, 河井和夫, 竹島泰弘, 飯島一誠, 松尾雅文
    (一社)日本小児腎臓病学会, 01 Jun. 2009, 日本小児腎臓病学会雑誌, 22(1) (1), 138 - 138, Japanese

  • IPEX症候群に微小変化型ネフローゼ症候群を合併した1症例
    橋村裕也, 野津寛大, 神田杏子, 早川晶, 竹島泰弘, 飯島一誠, 松尾雅文, 中西浩一, 吉川徳茂
    (一社)日本小児腎臓病学会, 01 Jun. 2009, 日本小児腎臓病学会雑誌, 22(1) (1), 98 - 98, Japanese

  • 戸川 寛子, 中西 浩一, 島 友子, 佐古 まゆみ, 宮嶋 正康, 野津 寛大, 飯島 一誠, 吉原 大輔, 長尾 枝澄香, 吉川 徳茂
    (一社)日本小児腎臓病学会, Jun. 2009, 日本小児腎臓病学会雑誌, 22(1Suppl.) (1Suppl.), 138 - 138, Japanese

  • 腎移植後巣状分節性糸球体硬化症(FSGS)再発高リスク小児例に対する腎移植前予防的治療の試み
    藤井 寛, 近本 裕子, 石塚 喜世伸, 梶保 祐子, 倉山 亮太, 藤木 拓磨, 野津 寛大, 清水 真樹, 香美 祥二, 田中 亮二郎, 石田 英樹, 田邉 一成, 秋岡 祐子, 黒田 奈緒, 服部 元史
    (一社)日本小児腎臓病学会, Jun. 2009, 日本小児腎臓病学会雑誌, 22(1Suppl.) (1Suppl.), 104 - 104, Japanese

  • 【腎・泌尿器疾患の診断・治療Update】 腎疾患の遺伝子診断 どこまで明らかにされたか?Alport症候群を中心に
    Nozu Kandai, Iijima Kazumoto
    日本小児医事出版社, Jun. 2009, 小児科臨床, 62巻, 6号, pp. 1039-1044(6) (6), 1037 - 1071, Japanese
    Introduction scientific journal

  • ヒトARPKD相同遺伝子ラットモデルにおける尿細管部位特異的嚢胞形成
    戸川 寛子, 中西 浩一, 島 友子, 佐古 まゆみ, 宮嶋 正康, 野津 寛大, 飯島 一誠, 吉原 大輔, 長尾 枝澄香, 吉川 徳茂
    (一社)日本腎臓学会, Apr. 2009, 日本腎臓学会誌, 51(3) (3), 272 - 272, Japanese

  • 【小児の症候群】 腎・泌尿器 Gitelman症候群
    Nozu Kandai
    Apr. 2009, 小児科診療, 72巻, 増刊, pp. 377-377, Japanese
    Introduction scientific journal

  • 【小児の症候群】 腎・泌尿器 Bartter症候群
    Nozu Kandai
    診断と治療社, Apr. 2009, 小児科診療, 72巻, 増刊, pp. 370-370, 367 - 395, Japanese
    Introduction scientific journal

  • Nozu Kandai, Iijima Kazumoto
    Bartter症候群(BS)とGitelman症候群(GS)は、低K血症、高レニン・アルドステロン血症を特徴とする遺伝性尿細管疾患である。近年、原因部位・遺伝子が特定され、BSは1型から4型まで分類可能となったが、原因遺伝子を特定できる施設は限られており臨床症状や検査所見で分類しているのが現状である。しかし、BS3型はGSと臨床症状や検査所見が類似する患者が存在するため、それのみでは診断を確定することが困難な場合がある。そこで利尿剤負荷試験による障害部位特定により診断にいたる方法が見直されている。BS1型と2型は原因部位がヘンレループに存在するためフロセミドに反応せず、GSは遠位尿細管に存在するためサイアザイドに反応しない。しかし、BS3型は原因部位がヘンレループから遠位尿細管に及ぶため利尿剤負荷による反応が不明である。利尿剤負荷による正確な診断を得るためにも今後データの蓄積が必要である。(著者抄録)
    (一社)日本小児腎臓病学会, Apr. 2009, 日本小児腎臓病学会雑誌, 22巻, 1号, pp. 24-28(1) (1), 24 - 28, Japanese
    Introduction scientific journal

  • 【小児腎疾患の診断・治療戦略】 腎疾患の診断における遺伝子解析の有用性
    Nozu Kandai, Iijima Kazumoto
    Feb. 2009, 小児内科, 41巻, 2号, pp. 213-220, Japanese
    Introduction scientific journal

  • 【小児疾患診療のための病態生理】 腎・泌尿器疾患 Bartter症候群とGitelman症候群
    Nozu Kandai
    Nov. 2008, 小児内科, 40巻, 増刊, pp. 923-927, Japanese
    Introduction scientific journal

  • Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    Nov. 2008, 日本小児腎臓病学会雑誌, 21巻, 2号, pp. 117-121, Japanese
    [Refereed]
    Introduction scientific journal

  • 多重リスクに対し検討を重ね二次生体腎移植を行った巣状分節性糸球体硬化症の1小児例
    黒田 奈緒, 近本 裕子, 秋岡 祐子, 田邉 一成, 世川 修, 野村 実, 桑鶴 良平, 杉谷 篤, 野津 寛大, 服部 元史
    (一社)日本移植学会, Sep. 2008, 移植, 43(総会臨時) (総会臨時), 346 - 346, Japanese

  • 【小児病理 最近のトピックス】 小児腎疾患の遺伝子異常と病理 Alport症候群とWT1関連腎症を例として
    Nozu Kandai, Iijima Kazumoto
    Sep. 2008, 病理と臨床, 26巻, 9号, pp. 898-903, Japanese
    Introduction scientific journal

  • 横山 忠史, 清水 正樹, 小泉 晶一, 龍 泰治, 古市 賢吾, 和田 隆志, 太田 和秀, 長沖 優子, 伊川 泰広, 和田 英男, 貝藤 裕史, 野津 寛大
    14歳女。腹痛と嘔吐で急性腸炎と診断された。不安神経症のため自傷行為があり1ヵ月前まで睡眠薬等を内服していた。夕食後嘔吐と下腹部痛で受診し下腹部反跳痛、背部叩打痛を認め、腹部超音波とCTで両側腎腫大を認め、腎機能障害で急性糸球体腎炎を疑われ増悪したため紹介受診した。炎症反応の軽度上昇とUN、Crの上昇、尿酸値11.2mg/dlを認めた。尿所見は蛋白尿、潜血は軽度で輸液と利尿剤投与による保存的治療を開始したが腎機能は増悪しCr 5.1mg/dlまで上昇したため血液透析を施行した。間質性腎炎の可能性を考えステロイド投与を行ったがGaシンチにより腎臓への集積を認めず速やかに中止した。詳細な問診から腹痛が出現した日は短距離走やリレーに出場しており、これより運動後急性腎不全(ALPE)の可能性を考え造影CTを施行した。造影直後は腎臓に造影剤の流入を認めず、24時間、72時間後のCTで楔型の造影剤排泄遅延を認めた。また、回復期の腎生検組織は糸球体にほとんど変化なく尿細管間質ではfocalに尿細管壊死像を認めた。以上より、ALPEと診断し保存的治療を行い腎機能は改善し退院した。
    日本小児腎不全学会, Aug. 2008, 日本小児腎不全学会雑誌, 28, 205 - 207, Japanese

  • Bartter症候群の病因病態 遺伝子解析から見えてきたもの
    Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    日本小児科学会, Jul. 2008, 日本小児科学会雑誌, 112巻, 7号, pp. 1059-1067(7) (7), 1059 - 1067, Japanese
    [Refereed]
    Introduction scientific journal

  • 【透析トラブルQ&A】 透析患者の保育園、幼稚園、学校生活での注意点を教えてください
    Nozu Kandai
    May 2008, 腎と透析, 64巻, 5号, pp. 796-798, Japanese
    Introduction scientific journal

  • ゼラチンスポンジによる塞栓を行った腎生検後の仮性動脈瘤の1例
    川崎 竜太, 杉本 幸司, 野津 寛大, 前田 哲雄, 伊崎 健太, 山口 雅人, 藤井 正彦, 杉村 和朗
    (一社)日本インターベンショナルラジオロジー学会, Apr. 2008, IVR: Interventional Radiology, 23(2) (2), 217 - 217, Japanese

  • Bartter syndrome and Gitelman syndrome
    野津 寛大, 松尾 雅文, 飯島 一誠
    診断と治療社, Feb. 2008, The Journal of pediatric practice, 71(2) (2), 305 - 310, Japanese

  • Kazumoto Iijima, Ichiro Kamioka, Kandai Nozu
    Most cases of diarrhea-associated hemolytic uremic syndrome (D+HUS) are caused by Shiga toxin-producing bacteria. Shiga toxin-producing Escherichia coli (STEC) O157: H7 has the strongest association worldwide with HUS. A massive outbreak of E. coli O157: H7 infections in Sakai, Osaka, Japan, in 1996 raised public and medical awareness of STEC. However, most cases are sporadic or occur in small clusters. Indeed, more than 100 sporadic or small cluster cases of D+HUS occur every year in Japan. The use of antibiotics in patients with definite or possible enteric STEC infections is controversial; however, there has been no randomized controlled trial to date showing the effectiveness of antibiotics for the prevention of the development of HUS. Thus, most investigators in western countries believe that antibiotics should not be administered to patients with such infections, and the management of HUS remains supportive. There are no specific therapies to ameliorate the course of the disease, and vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhea. The best way to prevent HUS is to prevent primary infection by Shiga toxin-producing bacteria.
    SPRINGER, Feb. 2008, CLINICAL AND EXPERIMENTAL NEPHROLOGY, 12(1) (1), 16 - 19, English
    [Refereed]
    Book review

  • スプライシング異常が確認できたGitelman症候群の一例
    飯田 啓二, 野津 寛大, 高橋 裕, 置村 康彦, 加治 秀介, 松尾 雅文, 春日 雅人, 千原 和夫
    (一社)日本内分泌学会, Dec. 2007, 日本内分泌学会雑誌, 83(3) (3), 792 - 792, Japanese

  • Identification of 6 novel mutations in the COL4A5 gene of Japanese patients with X-linked alport syndrome
    R. Krol, K. Nozu, K. Kanda, H. Kaito, K. Nakanishi, N. Yoshikawa, K. Kamei, K. Iijima, M. Matsuo
    SPRINGER, Sep. 2007, PEDIATRIC NEPHROLOGY, 22(9) (9), 1492 - 1492, English
    Summary international conference

  • Transient elevation of plasma antidiuretic hormone level after kidney biopsy associated with iatrogenic hyponatremia or postoperative nausea and vomit
    K. Kanda, K. Nozu, H. Kaito, R. Krol, K. Nakanishi, N. Yoshikawa, K. Iijima, M. Matuo
    SPRINGER, Sep. 2007, PEDIATRIC NEPHROLOGY, 22(9) (9), 1524 - 1524, English
    Summary international conference

  • Molecular analysis of 5 Japanese patients with type III bartter syndrome
    K. Nozu, K. Nakanishi, N. Yoshikawa, H. Kaito, K. Kanda, R. Krol, K. Satomura, N. Shimizu, K. Iijima, M. Matsuo
    SPRINGER, Sep. 2007, PEDIATRIC NEPHROLOGY, 22(9) (9), 1488 - 1488, English
    Summary international conference

  • Bartter症候群、Gitelman症候群の遺伝子解析からみえてきたこと
    Nozu Kandai
    Sep. 2007, 腎と透析, 63巻, 3号, pp. 407-414, Japanese
    Introduction scientific journal

  • Long-term outcome of focal segmental glomerulosclerosis after living-related pediatric renal transplantation.
    Masashi Takeda, Yoji Hyodo, Toshiro Ishida, Takeshi Ishimura, Isao Hara, Kandai Nozu, Norishige Yoshikawa, Masato Fujisawa
    BLACKWELL PUBLISHING, May 2007, PEDIATRIC TRANSPLANTATION, 11, 85 - 85, English
    Summary international conference

  • Nozu Kandai
    Apr. 2007, 日本小児腎臓病学会雑誌, 20巻, 1号, pp. 21-25, Japanese
    Introduction scientific journal

  • 【腎・泌尿器疾患領域における遺伝子解析】 Bartter症候群
    Nozu Kandai
    (株)東京医学社, Dec. 2006, 腎と透析, 61巻, 6号, pp. 835-840(6) (6), 819 - 821, Japanese
    Introduction scientific journal

  • 加古 麻恵, 野津 寛大, 守屋 友加, 胡本 千穂, 中村 任, 大石 美惠, 西口 工司, 栄田 敏之, 松尾 雅文, 奥村 勝彦
    (一社)日本TDM学会, Apr. 2006, TDM研究, 23(2) (2), 89 - 90, Japanese

  • 巣状分節状糸球体硬化症のフォロー中に発症したBasedow病の1例
    西山敦史, 石橋和人, 藤田晃生, 神岡一郎, 野津寛大, 竹島泰弘, 松尾雅文, 八木麻理子
    (公社)日本小児科学会, 01 Apr. 2006, 日本小児科学会雑誌, 110(4) (4), 583 - 584, Japanese

  • T Fujita, K Nozu, K Iijima, Kamioka, I, K Yoshiya, R Tanaka, K Hamahira, K Nakanishi, N Yoshikawa, M Matsuo
    Atypical membranoproliferative glomerulonephritis (MPGN) has been reported to have a good prognosis when treated with corticosteroids. However, this recommendation is based on uncontrolled trials and is associated with many complications. The purpose of our study is to determine whether steroid therapy is indicated for atypical MPGN. The cases of seven patients with atypical MPGN are reported in this study. Urinary abnormalities of five of them were detected by urine screening at school, of two because of macrohematuria. Hypocomplementemia was noted in six patients. All but one patient were treated without corticosteroids, and five with angiotensin-converting enzyme inhibitors (ACEI) and/or the Chinese herbal medicine Sairei-to (TJ-114). One patient recovered spontaneously from proteinuria and was therefore not treated, and one who developed severe proteinuria during observation was treated with corticosteroids. After an average follow-up period of 10.0 years, five patients showed normal urinary findings, one had hematuria and one proteinuria. At the most recent follow-up, the renal function of all patients remained within the normal range, and serum C3 had returned to normal levels in five out of six. These findings suggest that the indication of steroid therapy for atypical MPGN should be re-examined, since most of the patients with atypical MPGN seem to have an excellent prognosis without treatment with corticosteroids.
    SPRINGER, Feb. 2006, PEDIATRIC NEPHROLOGY, 21(2) (2), 194 - 200, English
    Introduction scientific journal

  • 小児領域 Bartter症候群の表現型,遺伝子型の相関
    NOZU, kandai, MATSUO, Masafumi, IIJIMA,Kazumoto
    Jan. 2006, Annual Review腎臓, 2006巻, pp.180-189, Japanese
    Introduction scientific journal

  • 【ネフローゼ症候群のすべて】 基礎 実験モデル 糸球体透過性因子の最近の動向
    Nozu Kandai
    Dec. 2005, 腎と透析, 59巻, 増刊, pp. 72-76, Japanese
    Introduction scientific journal

  • K Nozu, K Iijima, T Sakaeda, K Okumura, K Nakanishi, N Yoshikawa, M Honda, M Ikeda, M Matsuo
    A single blood concentration measurement of Neoral 2 h after administration (C2) is a new concept in therapeutic drug monitoring (TDM). In most adult patients, the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral administration. Therefore, monitoring the area under the concentration-time curve over the first 4 h post-dose ( AUC0 - 4) is considered to be the most reliable strategy for Neoral TDM. In addition, C2 is considered to be the most accurate predictor of AUC0 - 4, with which C2 correlates best. Thus, in adult patients, C2 monitoring is recommended as the best single-point TDM method for Neoral. However, in paediatric patients, the effectiveness of C2 monitoring is still unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in 60 patients ( 1 to 20 years old, mean age 7.42+/-7 years) who had nephrotic syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38 patients ( early peak group) and C3 or C4 in 22 patients ( late peak group). C2 in the late peak group was significantly lower than that in the early peak group (422+/-50.1 vs. 665+/-53.8 ng/ml, P = 0.0008), although the administered doses of Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the same standard as in the early peak group might result in an overdose of CyA in the late peak group. As the concentration peaked at 3 h or more after Neoral administration in the late peak group, AUC0 - 4 does not necessarily reflect the Neoral absorption profile. As more than 33% of the paediatric patients were in the late peak group, TDM by AUC0 - 4 or C2 should be used carefully in paediatric patients treated with Neoral.
    SPRINGER, Jul. 2005, PEDIATRIC NEPHROLOGY, 20(7) (7), 910 - 913, English
    [Refereed]
    Introduction scientific journal

  • 非典型的膜性増殖性糸球体腎炎の治療と予後
    藤田晃生, NOZU, kandai, 吉川徳茂
    金原出版, Jun. 2005, 小児科, 46巻, 7号, pp.1179-1184(7) (7), 1179 - 1184, Japanese
    Introduction scientific journal

  • Teguh Haryo Sasongko, Ahmad Hamim Sadewa, Pungky Ardani Kusuma, Martua Parlindungan, Damanik, LEE, Meijin, AYAKI, Hitoshi, NOZU, kandai, Akinobu Goto, MATSUO, Masafumi, NISHIO, Hisahide
    Background: The angiotensin converting enzyme (ACE) gene carries insertion (I)and deletion (D) polymorphism within its intron 16. The presence of D-allele in theACE gene has been reported as a probable genetic risk factor for idiopathic nephroticsyndrome
    神戸大学医学部, 2005, The Kobe Journal Of Medical Sciences, Vol. 51, No. 3-4, pp. 41-47(3) (3), 41 - 47, English
    [Refereed]
    Introduction scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 目でみる症例 小児IgA腎症
    Nozu Kandai
    南江堂, May 2004, 内科, 93巻, 5号, pp. 960-963(5) (5), 959 - 963, Japanese
    Introduction scientific journal

  • 【腎炎・ネフローゼ:そこが知りたい】 cyclosporineはトラフ値の測定がこれまで重要とされてましたが,最近はいかがですか?
    NOZU, kandai, IIJIMA,Kazumoto
    Feb. 2004, 小児内科, 36巻, 2号, pp. 330-333, Japanese
    Introduction scientific journal

  • Genetic linkage analysis of candidate loci in Japanese families with steroid resistant nephrotic syndrome.
    A Kitamura, T Hiroyasu, K Shoji, M Hattori, M Ikeda, M Honda, K Nozu, N Yoshikawa, Y Kuroda, T Doi, K Iijima
    LIPPINCOTT WILLIAMS & WILKINS, Nov. 2003, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 14, 103A - 103A, English
    Summary international conference

  • 28-04-03 小児患者におけるシクロスポリン C2 モニタリングに関する検討
    守屋 友加, 和田 敦, 中村 任, 栄田 敏之, 西口 工司, 西庄 京子, 野津 寛大, 田中 亮二郎, 飯島 一誠, 奥村 勝彦
    日本医療薬学会, 01 Sep. 2003, 日本医療薬学会年会講演要旨集, 13, 152 - 152, Japanese

  • 移植後リンパ球増殖性疾患（PTLD）の再発時にrituximabを投与し著効した1例
    NOZU, kandai, 田中亮二朗, NAKAMURA,Hajime, MATSUO, Masafumi, 吉矢邦彦, IIJIMA,Kazumoto
    2003, 日本小児腎不全学会雑誌, 23巻, 8, pp. 200-203, Japanese
    Introduction scientific journal

  • A new mutation of Na-K-2Cl cotransportor gene (NKCC2) in antenatal Bartter syndrome with renal failure.
    XJ Fu, AH Sadewa, K Yoshiya, K Nozu, R Tanaka, H Nakamura, M Matuo, H Nishio, K Iijima
    LIPPINCOTT WILLIAMS & WILKINS, Sep. 2002, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 13, 305A - 305A, English
    Summary international conference

  • Pharmacokineties of neutral in pediatric patients.
    K Nozu, T Sakaeda, T Kita, R Tanaka, H Nakamura, K Okumura, K Iijima
    LIPPINCOTT WILLIAMS & WILKINS, Sep. 2002, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 13, 631A - 631A, English
    Summary international conference

  • Total Parenteral Nutrition in Children with Acute Renal Failure
    野津 寛大, 田中 亮二郎, 吉矢 邦彦
    金原出版, Aug. 2002, 小児科, 43(8) (8), 1014 - 1021, Japanese

■ Lectures, oral presentations, etc.
  • 遺伝性腎疾患における遺伝子診断の現状とこれからの課題
    Nozu Kandai
    第47回日本腎臓学会東部学術集会, Oct. 2017, Japanese, 日本腎臓学会, 横浜, Domestic conference
    Invited oral presentation

  • シクロスポリンの効果は一時的であったACTN4新規遺伝子変異を伴うFSGS男児例
    櫻谷浩志, 藤永周一郎, Nozu Kandai
    第47回日本腎臓学会東部学術集会, Oct. 2017, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • The comprehensive gene screening for congenital, infantile, and steroid resistant nephrotic syndrome in Japan
    Nozu Kandai, Sakakibara N, Horinouchi T, Minamikawa Shogo, Yamamura Tomohiko, Kaito Hiroshi, Shima Y, Iijima Kazumoto
    ASN Kidney Week 2017, Oct. 2017, English, American Society of Nephrology, New Orleans, USA, International conference
    [Invited]
    Poster presentation

  • TGFBI関連眼腎症候群の1例：顆粒状角膜ジストロフィII型と腎症の合併例
    岩淵洋一, 森岡哲夫, 小山裕子, Nozu Kandai, Iijima Kazumoto, 成田一衛
    第47回日本腎臓学会東部学術集会, Oct. 2017, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 治療方針の決定に疾患パネル解析を用いたステロイド抵抗性ネフローゼ症候群の1例
    長野智那, Kaito Hiroshi, 堀之内智子, Minamikawa Shogo, Yamamura Tomohiko, Nozu Kandai, Iijima Kazumoto, 神吉直宙, 濱平陽史
    ・第38回日本小児腎不全学会, Sep. 2017, Japanese, 日本小児腎不全学会, 淡路, Domestic conference
    [Invited]
    Oral presentation

  • Alport症候群の病態生理と軽症化の試み
    Nozu Kandai
    ・第38回日本小児腎不全学会, Sep. 2017, Japanese, 日本小児腎不全学会, 淡路, Domestic conference
    [Invited]
    Invited oral presentation

  • Alport症候群の病理解析と治療法の開発
    Nozu Kandai
    第60回日本腎臓学会学術集会 サテライトシンポジウム, Jul. 2017, Japanese, 日本腎臓学会, 北海道, Domestic conference
    [Invited]
    Invited oral presentation

  • 臨床および病理学的にAlport症候群と診断した一例における分子生物学的検討
    三輪沙織, Nozu Kandai, 梅田千里, 掛川大輔, 山田哲史, 伊藤 亮, 村上仁彦, Minamikawa Shogo, Iijima Kazumoto, 平野大志
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 先天性ネフローゼ症候群/乳児ネフローゼ症候群およびステロイド抵抗性ネフローゼ症候群における網羅的遺伝子診断体制の構築
    Nozu Kandai, 堀之内智子, Yamamura Tomohiko, Minamikawa Shogo, 忍頂寺毅史, Kaito Hiroshi, 島 友子, 中西浩一, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • ゲノム情報を臨床へ―遺伝性腎疾患へのアプローチ―バイオサイエンスデータベースを使った解析手法
    Nozu Kandai
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Invited oral presentation

  • エクソンスキッピング療法によるアルポート症候群特異的療法治療法の開発
    Shono Akemi, Nozu Kandai, 小泉 誠, 大西朗之, 高石巨澄, Yamamura Tomohiko, Minamikawa Shogo, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • NGSターゲット遺伝子シークエンスパネルによるCAKUTおよびNPHの包括的原因遺伝子解析
    森貞直哉, Shono Akemi, Nozu Kandai, 忍頂寺毅史, 叶 明娟, 井藤奈央子, 神田祥一郎, 亀井宏一, 石倉健司, 伊藤秀一, 山本勝輔, 塚口裕康, 里村憲一, 田中亮二郎, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • minigeneを用いた遺伝性腎疾患におけるpathogenic splicing variantの同定
    Yamamura Tomohiko, Nozu Kandai, 久富隆太郎, 上田博章, 藤丸李可, 堀之内智子, Minamikawa Shogo, Shono Akemi, 忍頂寺毅史, Kaito Hiroshi, 中西浩一, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • Lowe症候群およびDent2の分子生物学的検討
    Minamikawa Shogo, Nozu Kandai, Yamamura Tomohiko, Kaito Hiroshi, 前川講平, 佐藤 亨, 原田真理, 五十嵐徹, 平本龍吾, 田中亮二郎, 松山 健, 長谷幸治, 沖 栄進, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • lgA腎症候群における降圧薬治療不応例に関する臨床病理学的検討
    忍頂寺毅史, 堀之内智子, Yamamura Tomohiko, Minamikawa Shogo, Kaito Hiroshi, Nozu Kandai, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • In vivoおよび in vitroの解析によりsplicing異常による疾患発症を証明したフィブロネクチン腎症の一例
    辻ゆり佳, Nozu Kandai, 堀之内智子, Yamamura Tomohiko, Minamikawa Shogo, 忍頂寺毅史, Kaito Hiroshi, 祖父江理, Hara Shigeo, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • Establishment of a comprehensive diagnostic method using next generation sequencer for the Alport syndrome
    Yamamura Tomohiko, Nozu Kandai, Horinouchi T, Manamikawa S, Shono Akemi, Ninchoji T, Kaito Hiroshi, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • C1qの沈着を伴った常染色体優性Alport症候群の一例
    波多江健, 檜山麻衣子, 黒木理恵, 中川兼康, Nozu Kandai, Iijima Kazumoto
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • Alport症候群9家計の臨床的検討
    大串栄彦, 大塚泰史, 溝端理恵, 陣内久美子, 岡 政史, 佐藤忠司, Nozu Kandai, Iijima Kazumoto, 松尾宗明
    第52回日本小児腎臓病学会, Jun. 2017, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 小児lgA腎症における糸球体毛細管係蹄（cap）lgA沈着の臨床病理学的検討
    島友子, 中西浩一, 佐藤匡, 浜武継, 向山弘展, 戸川寛子, Kaito Hiroshi, Nozu Kandai, 田中亮二郎, Iijima Kazumoto, 吉川徳茂
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 女性Dent病における遺伝学的背景
    Minamikawa Shogo, Nozu Kandai, 堀之内智子, Yamamura Tomohiko, 忍頂寺毅史, 島友子, 中西浩一, 服部益治, 神田杏子, 田中亮二郎, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 治療方針決定の一助に疾患パネル解析を用いたステロイド抵抗性ネフローゼ症候群の1例
    長野智那, Kaito Hiroshi, 堀之内智子, Minamikawa Shogo, Yamamura Tomohiko, Nozu Kandai, 神吉直宙, 濱平陽史, Iijima Kazumoto
    日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • 次世代シークエンサーを用いたAlport症候群の網羅的診断法の確立
    Yamamura Tomohiko, Nozu Kandai, 堀之内智子, Minamikawa Shogo, Shono Akemi, 忍頂寺毅史, Kaito Hiroshi, 中西浩一, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 下痢関連溶血性尿毒症症候群(D+HUS)の急性期経過と予後
    忍頂寺毅史, Yamamura Tomohiko, Minamikawa Shogo, Kaito Hiroshi, Nozu Kandai, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference
    [Invited]
    Invited oral presentation

  • 医師主導治験でリツキシマブ投与を行った小児期発症難治性ネフローゼ症候群患者の長期予後
    亀井宏一, 石倉健司, 佐古まゆみ, 綾邦彦, 田中亮二郎, Nozu Kandai, Kaito Hiroshi, 中西浩一, 大友義之, 三浦健一郎, 高橋昌里, 森本哲司, 久保田亘, 伊藤秀一, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝性腎疾患の研究から学んだ大切なこと－研究の楽しさと臨床へのフィードバック－
    Nozu Kandai
    第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference
    [Invited]
    Invited oral presentation

  • 遺伝性疾患におけるエクソンスキッピング療法の現状と腎疾患への応用の可能性
    Nozu Kandai, Shono Akemi, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Invited oral presentation

  • The utility of urinary CD80 as a diagnostic maker in patients with renal disease
    Minamikawa Shogo, Nozu Kandai, Horinouchi T, Yamamura Tomohiko, Kaito Hiroshi, Shima Y, Iijima Kazumoto
    Asian Congress of Pediatric Nephrology 2017 & 39th Malaysian Pediatric Association Annual Congress,, May 2017, English, Kuala Lumpur, Malaysia., International conference
    [Invited]
    Oral presentation

  • OFD1ヘミ接合性変異を認めたネフロン癆関連シリオパチーの1男児例
    森貞直哉, 清水順也, Shono Akemi, Ikeda Mariko, Nozu Kandai, Iijima Kazumoto
    日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • NPH・MCKDの遺伝子診断と病型
    森貞直哉, Nozu Kandai, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Invited oral presentation

  • NGSターゲット遺伝子シークエンスパネルによるCAKUTおよびNPHの包括的原因遺伝子解析
    森貞直哉, Shono Akemi, Nozu Kandai, 忍頂寺毅史, 田中亮二郎, Iijima Kazumoto
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • In vitro splicing assays to detecy intronic pathogenic variants in inherited kidney disease
    Nozu Kandai, Horinouchi T, Minamikawa Shogo, Yamamura Tomohiko, Ninchoji T, Kaito Hiroshi, Yoshikawa N, Iijima Kazumoto
    50th Anniversary Meeting of the European Society for Pediatric Nephrology, May 2017, English, The International Pediatric Nephrology Association, Glasgou, Scotland, International conference
    [Invited]
    Poster presentation

  • Functional splicing analysis in an infantile case of atypical hemolytic uremic syndrome caused by digenic mutations in C3 and MCP genes.
    Yamamura Tomohiko, Nozu Kandai, Horinouchi T, Minamikawa Shogo, Ueda H, Fujimaru R, Shima Y, Ninchoji T, Kaito Hiroshi, Iijima Kazumoto
    ASN Kidney Week 2017 Annual Meeting, May 2017, English, American Society of Nephrology, New Orleans, USA, International conference
    [Invited]
    Poster presentation

  • A variety of phenotypes reflected by genotypes and laminin β2 sxpression on glomerulus in Pierson syndrome
    Minamikawa Shogo, Nozu Kandai, Horinouchi T, Yamamura Tomohiko, Ninchoji T, Kaito Hiroshi, Yoshikawa N, Iijima Kazumoto
    50th Anniversary Meeting of the European Society for Pediatric Nephrology, May 2017, English, The International Pediatric Nephrology Association, Glasgou, Scotland, International conference
    [Invited]
    Poster presentation

  • Alport症候群の臨床遺伝学的研究
    Nozu Kandai
    第60回日本腎臓学会, May 2017, Japanese, 日本腎臓学会, 仙台, Domestic conference
    [Invited]
    Invited oral presentation

  • A comprehensive diagnosis by targeted sequencing for clinically suspectsd alport syndrome patients in Japan
    Yamamura Tomohiko, Nozu Kandai, Horinouchi T, Minamikawa Shogo, Shono Akemi, Ninchoji T, Kaito Hiroshi, Shima Y, Iijima Kazumoto
    Asian Congress of Pediatric Nephrology 2017 & 39th Malaysian Pediatric Association Annual Congress,, May 2017, English, Kuala Lumpur, Malaysia., International conference
    [Invited]
    Poster presentation

  • Genetic approach for the nephrotic syndrome
    Nozu Kandai
    The15th Japan-Korea-China Pediatrics Nephrology Seminar 2017, Apr. 2017, English, International Pediatric Nephrology Association, Tokyo, Japan, International conference
    [Invited]
    Invited oral presentation

  • Diagnostic strategy for inherited hypomagnesemia
    Horinouchi T, Nozu Kandai, Kamei K, Shima Y, Yamamura Tomohiko, Minamikawa Shogo, Ninchoji T, Kaito Hiroshi, Iijima Kazumoto
    The15th Japan-Korea-China Pediatrics Nephrology Seminar 2017, Apr. 2017, English, International Pediatric Nephrology Association, Tokyo, Japan, International conference
    [Invited]
    Oral presentation

  • Clinical characteristics in Gitelman syndrome
    Junya Fujimura, Nozu Kandai, China Nagano, Nana Sakakibara, Keita Nakanishi, Tomoko Horinouchi, Minamikawa Shogo, Yamamura Tomohiko, Kaito Hiroshi, Iijima Kazumoto
    ISN Frontiers Meeting 2018, Feb. 2017, English, 国際腎臓学会, 東京, International conference
    [Invited]
    Poster presentation

  • The comprehensive gene screening for congenital, infantile, and steroid resistant nephrotic syndrome in Japan
    Nozu Kandai, Sakakibara N, Horinouchi T, Minamikawa Shogo, Yamamura Tomohiko, Kaito Hiroshi, Shima Y, Iijima Kazumoto
    ISN Frontiers Meetings 2018, Jan. 2017, English, 国際腎臓学会, 東京, International conference
    [Invited]
    Poster presentation

  • Characteristics of genetic and biomolecular backgrounds in patients with LAMB2 related nephropathy
    Minamikawa Shogo, Nozu Kandai, Nakanishi K, Yamamura Tomohiko, Ninchoji Takeshi, Shima Y, Nakanisni K, Iijima Kazumoto
    Kidney Week of the American Society of Nephrology 2016, Nov. 2016, English, Kidney Week of the American Society of Nephrology, Chicago, USA, International conference
    [Invited]
    Oral presentation

  • 当院における小児腎移植の現状と課題
    藤村順也, 中西啓太, Minamikawa Shogo, Yamamura Tomohiko, Nozu Kandai, Ishimura Takeshi, Fujisawa Masato, Iijima Kazumoto
    第38回日本小児腎不全学会学術集会, Oct. 2016, Japanese, 日本小児腎不全学会, 岐阜, Domestic conference
    [Invited]
    Oral presentation

  • Genetic and clinical characteristics of female X-linked Alport Syndrome: 267case study
    Yamamura Tomohiko, Nozu Kandai, Nakanishi K, Horinouchi T, Fujimura J, Minamikawa Shogo, Kamiyoshi N, Ninchoji Takeshi, Kaito Hiroshi, Morisada N, Nakanishi K, Yoshikawa N, Iijima Kazumoto
    17thCongress of the International Pediatric Nephrology Association, Sep. 2016, English, Congress of the International Pediatric Nephrology Association, Iguazu, Brazil, International conference
    [Invited]
    Oral presentation

  • 24時間自由行動下血圧測定が高血圧診療に有用であった1例
    Yamamura Tomohiko, 中西啓太, 藤村順也, Minamikawa Shogo, Ninchoji Takeshi, Nozu Kandai, Iijima Kazumoto
    第 269 回 日本小児科学会兵庫県地方会, Sep. 2016, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference
    [Invited]
    Oral presentation

  • 平滑筋腫を合併したアルポート症候群の臨床像と遺伝子学的検討
    Minamikawa Shogo, Nozu Kandai, 中西啓太, 藤村順也, 堀之内智子, 神吉直宙, Ninchoji Takeshi, 長野智那, 後藤芳充, 平野大志, 藤永周一郎, 高橋英彦, 森下高弘, 森貞直哉, 田村雅仁, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • 直腸カルチノイドと頭蓋咽頭腫を認めたアルポート症候群の一例
    藤丸李可, 久富隆太郎, 熊谷雄介, 上田博章, 神吉直宙, Nozu Kandai, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • 腎炎の急性期治療 ACE-I,ARBの使用の可否 血清アルブミン値と病理組織所見に基づいた紫斑病性腎炎の治療戦略
    Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Invited oral presentation

  • 小児早期発症ステロイド抵抗性ネフローゼ症候群におけるNUP107変異の同定
    塚口裕康, 三宅紀子, 輿水江里子, Shono Akemi, Nozu Kandai, 秋岡祐子, 服部元史, 香美祥二, Iijima Kazumoto, 松本直通
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • 女性のDent病患者者2例における発症機序に関する考察
    Minamikawa Shogo, Nozu Kandai, 中西啓太, 藤村順也, 堀之内智子, Yamamura Tomohiko, 神吉直宙, Ninchoji Takeshi, 島 友子, 中西浩一, 服部益治, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • 次世代シークエンサーにて診断に至ったSDCCAG8変異によるネフロン癆の女児例
    中西啓太, Ninchoji Takeshi, 藤村順也, 堀之内智子, Minamikawa Shogo, Yamamura Tomohiko, 神吉直宙, 石森真吾, Nozu Kandai, 森貞直哉, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • 下痢関連溶血性尿毒症症候群（D+HUS）の急性期経過と予後
    Ninchoji Takeshi, Nozu Kandai, 中西啓太, 藤村順也, 堀之内智子, Minamikawa Shogo, Yamamura Tomohiko, 神吉直宙, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • ネフローゼ症候群と遺伝子－どこまで分かっているか、どのような場合遺伝子診断が必要か－
    Nozu Kandai, 森貞直哉, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Invited oral presentation

  • ターゲットシークエンス法による常染色体優性Alport症候群診断法の確立および遺伝学的背景、臨床的、病理学的検討
    神吉直宙, Nozu Kandai, 中西啓太, 堀之内智子, 藤村順也, Minamikawa Shogo, Yamamura Tomohiko, 松野下夏樹, Ninchoji Takeshi, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • エビデンスから見たネフローゼ‐Evidence-based treatment for nephrotic syndrome up to date－
    Nozu Kandai, 森貞直哉, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • X染色体連鎖型Alport症候群女性267例の遺伝学的・臨床的検討
    Yamamura Tomohiko, Nozu Kandai, 中西啓太, 堀之内智子, 藤村順也, Minamikawa Shogo, 神吉直宙, Ninchoji Takeshi, Kaito Hiroshi, 森貞直哉, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第51回日本小児腎臓病学会学術集会, Jul. 2016, Japanese, 日本小児腎臓病学会, 愛知, Domestic conference
    [Invited]
    Oral presentation

  • CAKUT及び原因不明の小児期発症慢性腎機能障害患者への包括的原因遺伝子解析
    森貞 直哉, Nozu Kandai, Shono Akemi, Ninchoji Takeshi, 叶 明娟, 井藤 奈央子, 神田 祥一郎, 亀井 宏一, 石倉 健司, 伊藤 秀一, 山本 勝輔, 里村 憲一, 服部 元史, 田中 亮二郎, Nishio Hisahide, Iijima Kazumoto
    The 51st Annual Meeting of the Japanese Society for Pediatric Nephrology, Jul. 2016, Japanese, The Japanese Society for Pediatric Nephrology, 名古屋, Domestic conference
    [Invited]
    Oral presentation

  • 当院の染色体優位性アルポート症候群の臨床病理学的特徴
    今福 礼, 澤 直樹, 川田 真宏, 平松里佳子, 長谷川詠子, 田中希穂, 乳原善文, 大橋健一, Nozu Kandai, 高市憲明
    第59回日本腎臓学会学術総会, Jun. 2016, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 男女共同参画委員会企画：遺伝性腎疾患
    Nozu Kandai, 森貞直哉, Iijima Kazumoto
    第59回日本腎臓学会学術総会, Jun. 2016, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Invited oral presentation

  • 小児微少変化・巣状分節性糸球体硬化症の治療戦略
    Iijima Kazumoto, Nozu Kandai, 佐古まゆみ, 中西浩一, 吉川徳茂
    第59回日本腎臓学会学術総会, Jun. 2016, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Invited oral presentation

  • 小児早期発症ステロイド抵抗性ネフローゼ症候群におけるNUP107変異の同定
    塚口裕康, 三宅紀子, 輿水江里子, Shono Akemi, Nozu Kandai, 秋岡祐子, 服部元史, 香美祥二, Iijima Kazumoto, 松本直通
    第59回日本腎臓学会学術総会, Jun. 2016, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 次世代シークエンサー（NGS）による染色体優性Alport症候群診断法の確立および臨床的、病理学的検討
    Yamamura Tomohiko, Nozu Kandai, Minamikawa Shogo, 神吉直宙, Ninchoji Takeshi, Iijima Kazumoto
    第59回日本腎臓学会学術総会, Jun. 2016, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 両アレル性NUP107変異は早期小児発症ステロイド抵抗性ネフローゼ症候群を引き起こ す
    三宅紀子, 塚口裕康, 輿水江里子, Shono Akemi, Nozu Kandai, 秋岡祐子, 服部元史, Iijima Kazumoto, 松本直通
    第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference
    [Invited]
    Oral presentation

  • 直腸カルチノイドと頭蓋咽頭腫を認めたアルポート症候群の一例
    久富隆太郎, 熊谷雄介, 橋本有紀子, 上田博章, 神吉直宙, Nozu Kandai, Iijima Kazumoto, 佐藤 亨, 藤丸季可
    第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference
    [Invited]
    Oral presentation

  • 成長障害の経過観察中に四肢麻痺をきたし診断に至った尿細管性アシドーシスの1例
    藤村順也, Ninchoji Takeshi, 中西啓太, 堀之内智子, Minamikawa Shogo, Yamamura Tomohiko, Nozu Kandai, Iijima Kazumoto
    第268回日本小児科学会兵庫県地方会, May 2016, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • 腎移植後にウイルス関連の重症合併症を呈した4症例
    Minamikawa Shogo, 中西啓太, 藤村順也, 堀之内智子, Yamamura Tomohiko, 神吉直宙, Ninchoji Takeshi, Nozu Kandai, 早川 晶, Iijima Kazumoto
    第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference
    [Invited]
    Oral presentation

  • 次世代シークエンサーによる染色体優性Alport症候群診断法の確立
    神吉 直宙, Nozu Kandai, 中西 啓太, 堀之内 智子, 藤村 順也, Minamikawa Shogo, Yamamura Tomohiko, 松野下夏樹, Ninchoji Takeshi, Iijima Kazumoto
    第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference
    [Invited]
    Oral presentation

  • 胃腸炎に伴う低K血症から診断に至ったGitelman症候群の兄妹例
    辻 健史, 河野好彦, 林 誠司, 加藤 徹, 近藤 勝, 長井典子, 早川文雄, 松野下夏樹, Nozu Kandai, Iijima Kazumoto
    第119回日本小児科学会学術集会, May 2016, Japanese, 日本小児科学会, 札幌, Domestic conference
    [Invited]
    Poster presentation

  • Pathological and genetic aspects of the siblings with congenital/infantile nephrotic syndrome
    Minamikawa Shogo, Nozu Kandai, Hara Shigeo, Nakanishi K, Fujimura J, Horiuchi T, Yamamura Tomohiko
    The 14th China-Japan-Korea Pediatric Nephrology Seminar 2016, May 2016, English, China-Japan-Korea Pediatric Nephrology Seminar, Beijing,, China, International conference
    [Invited]
    Oral presentation

  • The comprehensive genetic analysis of congenital anomalies of the kidney and urinary tract (CAKUT) in Japan.
    Naoya Morisada, Shono Akemi, Ikeda Mariko, Nozu Kandai, Koichi Kamei, Kenji Ishikura, Shuichi Ito, Ryojiro Tanaka, Nishio Hisahide, Iijima Kazumoto
    The 13th International Congress of Human Genetics, Apr. 2016, English, 第13回国際人類遺伝学会国内組織委員会、日本学術会議, 京都, International conference
    [Invited]
    Oral presentation

  • Gene targeting therapy for Alport syndrome.
    Nozu Kandai
    Pediatric Academic Societies (PAS) Annual Meeting 2016, Apr. 2016, English, Pediatric Academic Societies, Baltimore, USA, International conference
    [Invited]
    Invited oral presentation

  • 腎移植後にウイルス関連の重症合併症を呈した4症例
    Ninchoji Takeshi, 中西啓太, 南川将吾, 山村智彦, Kamiyoshi Naohiro, Nozu Kandai, Ishimura Takeshi, Hayakawa Akira, Fujisawa Masato, Iijima Kazumoto
    第37回日本小児腎不全学会学術集会, Nov. 2015, Japanese, 日本小児腎不全学会, 石川, Domestic conference
    Oral presentation

  • 小児腎疾患診療における遺伝学的アプローチ
    Iijima Kazumoto, Morisada Naoya, Nozu Kandai
    第37回日本小児腎不全学会学術集会, Nov. 2015, Japanese, 日本小児腎不全学会, 石川, Domestic conference
    Public discourse

  • 遺伝子解析により早期診断に至ったGitelman症候群の2例
    菅谷憲太, 只木弘美, 伊奈真一郎, 福冨崇浩, 村田宗紀, 和田芳雅, 早野聡子, 植田晶子, 粟生耕太, 友野順章, 松野下夏樹, Nozu Kandai, Iijima Kazumoto, 伊藤秀一
    第37回日本小児腎不全学会学術集会, Nov. 2015, Japanese, 日本小児腎不全学会, 石川, Domestic conference
    [Invited]
    Poster presentation

  • 異なる経過をたどった腸管出血性大腸菌による溶血性尿毒症症候群の姉妹例
    中西啓太, Ninchoji Takeshi, 南川将吾, 山村智彦, Kamiyoshi Naohiro, Nishiyama Masahiro, Toyoshima Daisaku, Nozu Kandai, 濱平陽史, Iijima Kazumoto
    第37回日本小児腎不全学会学術集会, Nov. 2015, Japanese, 日本小児腎不全学会, 石川, Domestic conference
    Oral presentation

  • Somatic Mosaicism and Variant Frequency Detected by Next Generation Sequencing in X Linked Alport Syndrome.
    Kamiyoshi Naohiro, Nozu Kandai, Fu X.J, Yamamura Tomohiko, Minamikawa Syogo, Ninchoji Takeshi, Iijima Kazumoto
    Kidney Week 2015, Nov. 2015, English, American Society of Nephrology, San Diego, アメリカ, International conference
    [Invited]
    Poster presentation

  • Comprehensive Approach to Understand Human Renal Development Based on the Identification of Responsible Genes for CAKUT.
    Shono Akemi, Morisada Naoya, Nozu Kandai, Iijima Kazumoto
    Kidney Week 2015, Nov. 2015, English, American Society of Nephrology, San Diego, アメリカ, International conference
    [Invited]
    Oral presentation

  • 腎炎・ネフローゼ症候群の治療トピックス 難治性ネフローゼ症候群に対するリツキシマブ治療
    Iijima Kazumoto, Nozu Kandai, 佐古まゆみ
    第45回日本腎臓学会西部学術大会, Oct. 2015, Japanese, 日本腎臓学会, 金沢, Domestic conference
    Public symposium

  • Target gene sequencing panel を用いた先天性腎尿路奇形症候群(CAKUT)の網羅的遺伝子解析
    Morisada Naoya, 庄野朱美, Nozu Kandai, 叶 明娟, 神田祥一郎, 井藤奈央子, 亀井宏一, 伊藤秀一, 山本勝輔, 里村憲一, 田中亮二郎, Nishio Hisahide, Iijima Kazumoto
    日本人類遺伝学会 第60回大会, Oct. 2015, Japanese, 日本人類遺伝学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 重度の神経学的後遺症を残した腸管出血性大腸菌による溶血性尿毒症症候群の1 女児例
    中西啓太, 南川将吾, 山村智彦, Kamiyoshi Naohiro, Nishiyama Masahiro, Ninchoji Takeshi, Toyoshima Daisaku, Nozu Kandai, 濱平陽史, Iijima Kazumoto
    第266 回 日本小児科学会兵庫県地方会, Sep. 2015, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference
    Oral presentation

  • Genetic, pathological and clinical backgrounds in autosomal dominant Alport syndrome.
    Nozu Kandai, Kamiyoshi Naohiro, Matsunoshita Natsuki, Minamikawa Syogo, Yamamura Tomohiko, Ninchoji Takeshi, Tanaka Ryojirou, Nakanishi Keita, Yoshikawa N, Iijima Kazumoto
    48th Annual Scientific Meeting of the European Society for Pediatric Nephrology, Sep. 2015, English, ESPN, Brussels, ベルギー, International conference
    [Invited]
    Poster presentation

  • 低カリウム血症、代謝性アルカローシスを呈した常染色体優性低カルシウム血症の一例
    Kamiyoshi Naohiro, Nozu Kandai, 南川将吾, 山村智彦, 松野下夏樹, 大坪裕美, Ninchoji Takeshi, Kaito Hiroshi, 浦濱善倫, Iijima Kazumoto
    日本小児腎臓病学会学術集会 第50回記念大会, Jun. 2015, Japanese, 日本小児腎臓病学会, 神戸, Domestic conference
    Oral presentation

  • 常染色体優性Alport症候群の遺伝学的背景と臨床像
    Kamiyoshi Naohiro, Nozu Kandai, 南川将吾, 山村智彦, 松野下夏樹, 大坪裕美, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    第58回日本腎臓学会学術総会, Jun. 2015, Japanese, 日本腎臓学会, 名古屋, Domestic conference
    Oral presentation

  • 常染色体優性Alport症候群における遺伝学的背景および臨床的、病理学的検討
    Kamiyoshi Naohiro, Nozu Kandai, 南川将吾, 山村智彦, 松野下夏樹, 大坪裕美, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    日本小児腎臓病学会学術集会 第50回記念大会, Jun. 2015, Japanese, 日本小児腎臓病学会, 神戸, Domestic conference
    Oral presentation

  • 小児特発性膜性腎症とPLA2Rの関連
    中川 拓, 白鳥孝俊, 神田杏子, 吉田牧子, Ninchoji Takeshi, Nozu Kandai, Iijima Kazumoto, Hara Shigeo, 田中亮二郎
    第58回日本腎臓学会学術総会, Jun. 2015, Japanese, 日本腎臓学会, 名古屋, Domestic conference
    [Invited]
    Poster presentation

  • びまん性メサンギウム細胞増殖を呈した特発性ネフローゼ症候群の臨床病理学的検討
    山村智彦, Ninchoji Takeshi, 南川将吾, Kamiyoshi Naohiro, 松野下夏樹, 大坪裕美, Nozu Kandai, 中西啓太, 吉川徳茂, Iijima Kazumoto
    日本小児腎臓病学会学術集会 第50回記念大会, Jun. 2015, Japanese, 日本小児腎臓病学会, 神戸, Domestic conference
    Oral presentation

  • Branchio-oto-renal (BOR) 症候群の原因遺伝子と腎症状に関する検討
    Morisada Naoya, Nozu Kandai, 松永達雄, Iijima Kazumoto
    第58回日本腎臓学会学術総会, Jun. 2015, Japanese, 日本腎臓学会, 名古屋, Domestic conference
    [Invited]
    Oral presentation

  • Branchio-oto-renal(BOR)症候群の原因遺伝子と腎症状に関する検討
    Morisada Naoya, Nozu Kandai, 松永達雄, Iijima Kazumoto
    日本小児腎臓病学会学術集会 第50回記念大会, Jun. 2015, Japanese, 日本小児腎臓病学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • Bartter症候群と臨床診断された先天性クロール下痢症の2例
    松野下夏樹, Nozu Kandai, 南川将吾, 山村智彦, Kamiyoshi Naohiro, 大坪裕美, Ninchoji Takeshi, 吉兼正英, 一木 貴, 河口亜津彩, 上村 治, Iijima Kazumoto
    日本小児腎臓病学会学術集会 第50回記念大会, Jun. 2015, Japanese, 日本小児腎臓病学会, 神戸, Domestic conference
    Oral presentation

  • 全身性エリテマトーデス様所見を呈したヒトパルボウイルスB19 感染症の1 例
    山村智彦, 南川将吾, Kamiyoshi Naohiro, Ninchoji Takeshi, 佐々木香織, Nozu Kandai, 近平雅嗣, 萩美貴, Iijima Kazumoto
    第265 回 日本小児科学会兵庫県地方会, May 2015, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference
    Oral presentation

  • Pathogenesis for hypokalemia in case with autosomal dominant hypocalcemia.
    Kamiyoshi Naohiro, Nozu Kandai, Minamikawa Syogo, Yamamura Tomohiko, Matsunoshita Natsuki, Otsubo Hiromi, Ninchoji Takeshi, Shima Y, Nakanishi Kosuke, Iijima Kazumoto
    The 13th Korea-China-Japan Pediatric Nephrology Seminar 2015, May 2015, English, 日韓 中小児腎臓セミナー事務局 小児腎臓セミナー事務局 小児腎臓セミナー事務局 小児腎臓セミナー事務局 小児腎臓セミナー事務局 小児腎臓セミナー事務局, 韓国, 韓国, International conference
    Oral presentation

  • Evidence-based treatment for Nephrotic syndrome
    Nozu Kandai
    The 11th Asian Society for Pediatric Research, Apr. 2015, English, Asian Society for Pediatric Research, 大阪, International conference
    [Invited]
    Invited oral presentation

  • Effectiveness of diagnostic algorithm for inherited hypomagnesemia.
    Kamiyoshi Naohiro, Nozu Kandai, Matsunoshita Natsuki, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    Ⅻ Asian Congress of Pediatric Nephrology, Dec. 2014, English, IPNA, New Delhi, India, International conference
    [Invited]
    Poster presentation

  • Differential diagnosis of Bartter/Gitelman syndrome and pseudo-disorder based on clinical characteristics.
    Matsunoshita Natsuki, Nozu Kandai, Kamiyoshi Naohiro, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    Ⅻ Asian Congress of Pediatric Nephrology, Dec. 2014, English, IPNA, New Delhi, India, International conference
    [Invited]
    Oral presentation

  • 染色体構造異常によるsyndromic CAKUT の原因遺伝子についての検討
    Morisada Naoya, Nozu Kandai, 亀井 宏一, 伊藤 秀一, 田中 亮二郎, 石川 智朗, 足立 昌夫, 野田 俊輔, 石黒 利佳, 関根 孝司, 小崎 健次郎, Iijima Kazumoto
    第59回日本人類遺伝学会, Nov. 2014, Japanese, 日本人類遺伝学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • Smad3 Gene Deletion Ameliorates Cyst Formation and Interstitial Fibrosis in cpk Mouce, a Model of ARPKD.
    Taketsugu Hama, Koichi Nakanishi, Hironobu Mukaiyama, Hiroko Togawa, Masashi Sato, Yuko Shima, Masayasu Miyajima, Nozu Kandai, Shizuko Nagao, Hisahide Takahashi, Iijima Kazumoto, Norishige Yoshikawa
    American Society of Nephrology Kidney Week 2014, Nov. 2014, English, ASN, Philadelphia, USA, International conference
    [Invited]
    Poster presentation

  • Autosomal Dominant Alport Syndrome: Molecular Analysis of the COL4A3/COL4A4 Genes and Clinical Outcome.
    Kamiyoshi Naohiro, Nozu Kandai, Matsunoshita Natsuki, Hiromi Ohtsubo, Ninchoji Takeshi, Kaito Hiroshi, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    American Society of Nephrology Kidney Week 2014, Nov. 2014, English, ASN, Philadelphia, USA, International conference
    [Invited]
    Poster presentation

  • ステロイド及びシクロスポリンで完全寛解に至った巣状分節性糸球体硬化症collapsing variantの1例
    南川 将吾, Ninchoji Takeshi, Kamiyoshi Naohiro, Matsunoshita Natsuki, 大坪 裕美, Kaito Hiroshi, Hara Shigeo, Nozu Kandai, Iijima Kazumoto
    第36回日本小児腎不全学会学術集会, Oct. 2014, Japanese, 日本小児腎不全学会, 松江, Domestic conference
    [Invited]
    Oral presentation

  • The comprehensive genetic analysis of congenital anomalies of kidney and urinary tract (CAKUT) in Japan.
    Morisada Naoya, Ikeda Mariko, Nozu Kandai, Akemi Shono, Koichi Kamei, Syuichi Ito, Ryojiro Tanaka, Iijima Kazumoto
    The American Society of Human Genetics, Oct. 2014, English, ASHG, San Diego, USA, International conference
    [Invited]
    Poster presentation

  • トピラマート開始後著明な尿細管性アシドーシスと低身長の増悪を認めた一例
    南川 将吾, Kamiyoshi Naohiro, Matsunoshita Natsuki, Lee Tomoko, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, 八木 麻理子, 竹島 泰弘, Iijima Kazumoto
    第263回日本小児科学会兵庫県地方会, Sep. 2014, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference
    Oral presentation

  • X-linked Alport syndrome patients caused by atypical splicing mutations in COL4A5.
    Nozu Kandai, Morisada Naoya, Kaito Hiroshi, Ninchoji Takeshi, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    47th Annual Scientific Meeting of the European Society for Pediatric Nephrology, Sep. 2014, English, ESPN, PORTO, Portugal, International conference
    [Invited]
    Oral presentation

  • The comprehensive genetic analysis of CAKUT in Japan.
    Morisada Naoya, Nozu Kandai, Akemi Shono, Ninchoji Takeshi, Kaito Hiroshi, Koichi Kamei, Syuichi Ito, Ryojiro Tanaka, Iijima Kazumoto
    47th Annual Scientific Meeting of the European Society for Pediatric Nephrology, Sep. 2014, English, ESPN, PORTO, Portugal, International conference
    [Invited]
    Oral presentation

  • 本邦におけるCAKUT包括的原因遺伝子解析システムの構築
    Morisada Naoya, 庄野 朱美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, 亀井 宏一, 伊藤 秀一, 田中 亮二郎, Iijima Kazumoto
    第57回日本腎臓学会学術総会, Jul. 2014, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝性塩類喪失性尿細管機能異常症とその偽性症例の臨床的差異に関する検討
    Matsunoshita Natsuki, Nozu Kandai, Kamiyoshi Naohiro, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    第57回日本腎臓学会学術総会, Jul. 2014, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • フィブロネクチン腎症におけるFN1遺伝子変異の同定およびその機能解析に関する研究
    大坪 裕美, Nozu Kandai, Kamiyoshi Naohiro, Matsunoshita Natsuki, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    第57回日本腎臓学会学術総会, Jul. 2014, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • BartterおよびGitelman症候群に関する全国疫学調査
    Kaito Hiroshi, Nozu Kandai, Morisada Naoya, Iijima Kazumoto
    第57回日本腎臓学会学術総会, Jul. 2014, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • ｃｐｋマウスARPKDモデルにおける病的Smad3リン酸化
    浜 武継, 中西 浩一, 向山 弘展, 戸川 寛子, 佐藤 匡, 島 友子, 宮嶋 正康, Nozu Kandai, 高橋 久英, 長尾 枝澄香, Iijima Kazumoto, 吉川 徳茂
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • 微少蛋白尿を呈する小児IｇA腎症の長期予後
    比嘉 明日美, 島 友子, 浜 武継, 佐藤 匡, 向山 弘展, 戸川 寛子, 田中 亮二郎, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, 中西 浩一, 吉川 徳茂
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • 低カリウム血性横紋筋融解症を合併したGitelman症候群の男児例
    宮本 学, 福田 啓伸, 大和田 葉子, 鈴木 綾乃, 加藤 正也, 佐藤 雄也, 福島 啓太郎, Nozu Kandai, Iijima Kazumoto, 有阪 治
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • 初診時高血圧を呈さず特発性ネフローゼ症候群との鑑別を要した腎血管性高血圧の1例
    Kamiyoshi Naohiro, Ninchoji Takeshi, Matsunoshita Natsuki, 大坪 裕美, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝性塩類喪失性尿細管機能異常症とその偽性症例の臨床的差異に関する検討
    Matsunoshita Natsuki, Nozu Kandai, Kamiyoshi Naohiro, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • フィブロネクチン腎症（FN）におけるFN1遺伝子変異の同定およびその機能解析に関する研究
    大坪 裕美, Okada Taro, Kajimoto Taketoshi, Nozu Kandai, Kamiyoshi Naohiro, Matsunoshita Natsuki, Ninchoji Takeshi, Kaito Hiroshi, Nakamura Shun-ichi, Iijima Kazumoto
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • アルポート症候群―重症・軽症を規定する因子に関する再考―
    Nozu Kandai
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Invited oral presentation

  • Effective application of fibrin glue to prevent pericatheter leakage in peritoneal dialysis: a preliminary trial
    Hisamatsu Chieko, Kosaku Maeda, Yosuke Aida, Masao Yasufuku, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Eiji Nishijima
    15th European Congress of Paediatric Surgery, Jun. 2014, English, European Paediatric Surgeons' Association, Dublin, Ireland, International conference
    [Invited]
    Poster presentation

  • ACE阻害剤の投与により急性腎障害を認めたBartter症候群3型の1例
    鈴木 慎二, 長尾 竜兵, 赤羽 麻衣, 千代反田 雅子, 三浦 太郎, 熊田 篤, 柏木 保代, 河島 尚志, Nozu Kandai, Iijima Kazumoto
    第49回日本小児腎臓病学会学術集会, Jun. 2014, Japanese, 日本小児腎臓病学会, 秋田, Domestic conference
    [Invited]
    Oral presentation

  • 小児腹膜透析カテーテル留置後に生じた外科的合併症の検討
    Hisamatsu Chieko, 會田 洋輔, 前田 貢作, 安福 正男, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, 西島 栄治
    第51回日本小児外科学会学術集会, May 2014, Japanese, 日本小児外科学会, 大阪, Domestic conference
    [Invited]
    Poster presentation

  • 学校検尿で発見され、緩徐な経過を辿った特発性ネフローゼ症候群の1例
    南川 将吾, Kamiyoshi Naohiro, Matsunoshita Natsuki, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第262回日本小児科学会兵庫県地方会, May 2014, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference
    Oral presentation

  • シクロスポリン投与下に再発をきたしたステロイド感受性ネフローゼ症候群の長期予後
    Ninchoji Takeshi, Kaito Hiroshi, Kamiyoshi Naohiro, Matsunoshita Natsuki, 大坪 裕美, Nozu Kandai, 中西 浩一, 吉川 徳茂, Iijima Kazumoto
    第117回日本小児科学会学術集会, Apr. 2014, Japanese, 日本小児科学会, 名古屋, Domestic conference
    [Invited]
    Oral presentation

  • 再発直後に肺炎球菌による敗血症を合併したネフローゼ症候群の一例
    Kamiyoshi Naohiro, Matsunoshita Natsuki, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第261回日本小児科学会兵庫県地方会, Feb. 2014, Japanese, 日本小児科学会兵庫県地方会, 西宮, Domestic conference
    Oral presentation

  • Natural History and Protein Expression Pattern in Autosomal Recessive Alport Syndrome Based on the Comprehensive Strategy for Genetic Analysis.
    Kaito Hiroshi, Nozu Kandai, Masafumi Oka, Morisada Naoya, Ninchoji Takeshi, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    American Society of Nephrology KIDNEY WEEK, Nov. 2013, English, American Society of Nephrology, Atlanta, USA, International conference
    [Invited]
    Poster presentation

  • Investigation of Principal Mechanism for Renal Sodium Retention in Children with Idiopathic Nephrotic Syndrome.
    Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Taketsugu Hama, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    American Society of Nephrology KIDNEY WEEK, Nov. 2013, English, American Society of Nephrology, Atlanta, USA, International conference
    [Invited]
    Poster presentation

  • 腹膜透析中に急性虫垂炎を発症した3歳女児例
    神吉 直宙, Kaito Hiroshi, 松野下 夏樹, Ninchoji Takeshi, 大坪 裕美, Nozu Kandai, Hisamatsu Chieko, Iijima Kazumoto
    第35回日本小児腎不全学会学術集会, Oct. 2013, Japanese, 小児腎不全学会, 福島, Domestic conference
    [Invited]
    Oral presentation

  • Heterozygous microdeletion of 16q covering SALL1 and RPGRIP1L could be a novel contiguous gene syndrome with renal impairment.
    Morisada Naoya, Ikeda Mariko, Shingo Ishimori, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Masao Adachi, Takeshima Yasuhiro, Takashi Sekine, Iijima Kazumoto
    The American Society of Human Genetics, Oct. 2013, English, The American Society of Human Genetics, Boston, USA, International conference
    [Invited]
    Poster presentation

  • 発症後20年以上を経て再熱した紫斑病性腎炎の1例
    神吉 直宙, 松野下 夏樹, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, 西井 由佳, 北林 千津子, Iijima Kazumoto
    第260回日本小児科学会兵庫県地方会, Sep. 2013, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference
    Oral presentation

  • Multicenter, Double-Blind, Placebo-Controlled, Randomized Trial of Rituximab for the Treatment of Childhood-Onset Refractory nephrotic syndrome.
    Iijima Kazumoto, Mayumi Sako, Nozu Kandai, Nao Tsuchida, Ryojiro Tanaka, Kenji Ishikura, Shuichi Ito, Yasuo Ohashi
    The Sixteenth Congress of the International Pediatric Nephrology Association, Aug. 2013, English, International Pediatric Nephrology Association, Shanghai, China, International conference
    [Invited]
    Poster presentation

  • 常染色体優性多発性嚢胞腎(ADPKD)の間質線維化における上皮間葉系形質転換（ＥＭＴ）の関与に関する研究
    Nozu Kandai, Williams Sweeney, Emma Schwasingar, Nicholas Kampa, Iijima Kazumoto, Ellis Avner
    第48回日本小児腎臓病学会学術集会, Jun. 2013, Japanese, 日本小児腎臓病学会, 徳島, Domestic conference
    [Invited]
    Oral presentation

  • ネフローゼ症候群を呈したX染色体連鎖型Alport症候群の2例
    松野下 夏樹, Kaito Hiroshi, 石森 真吾, Ninchoji Takeshi, Nozu Kandai, 吉川 徳茂, Iijima Kazumoto
    第48回日本小児腎臓病学会学術集会, Jun. 2013, Japanese, 日本小児腎臓病学会, 徳島, Domestic conference
    [Invited]
    Poster presentation

  • 長期の寛解維持後に突然再発を繰り返したステロイド抵抗性ネフローゼ症候群の1例
    神吉 直宙, 松野下 夏樹, 大坪 裕美, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第259回日本小児科学会兵庫県地方会, May 2013, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference
    Oral presentation

  • The relation between steroid responsiveness and immunofluorescence findings in infant idiopathic nephrotic syndrome.
    Ninchoji Takeshi, Hiroshi Kaitoh, Natsuki Matsunoshita, Nozu Kandai, Koichi Nakanishi, Norishige Yoshikawa, Iijima Kazumoto
    European Renal Association-European Dialysis and Transplant Association, May 2013, English, ERA-EDTA, Istanbul, Turkey, International conference
    [Invited]
    Poster presentation

  • Genetical and clinical aspects of X-linked Alport syndrome in males with positive staining of the α5 (IV) chain.
    Hashimura Y, Nozu Kandai, Kaito Hiroshi, Ishimori S, Otsubo H, Hashimoto F, Ninchoji Takeshi, Morisada Naoya, Nakanishi K, Yoshikawa N, Iijima Kazumoto
    American Society of Nephrology, 2012 Kidney Week, Oct. 2012, English, San Diego, International conference
    [Invited]
    Oral presentation

  • Clinical characteristics and mutational pattern of genetically-proven Gitelman's syndrome.
    Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Nakanishi K, Yoshikawa N, Iijima Kazumoto
    American Society of Nephrology, 2012 Kidney Week, Oct. 2012, English, San Diego, International conference
    [Invited]
    Poster presentation

  • 尿中落下細胞の遺伝子解析と尿細管疾患の診断の実際－salt-losing tubulopathy を例に－
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第47回日本小児腎臓病学会学術集会, Jun. 2012, Japanese, 東京, Domestic conference
    [Invited]
    Invited oral presentation

  • 一過性に高度蛋白尿を呈し診断に苦慮したThin basement membrane diseaseの一例
    石森真吾, 大坪裕美, 橋本総子, Ninchoji Takeshi, 橋村裕也, Kaito Hiroshi, Morisada Naoya, Nozu Kandai, 吉川徳茂, Iijima Kazumoto
    第47回日本小児腎臓病学会学術集会, Jun. 2012, Japanese, 東京, Domestic conference
    [Invited]
    Poster presentation

  • X染色体連鎖型Alport症候群男性患者の腎重症度は、腎組織のα5染色パターンで予測可能である
    橋村裕也, Nozu Kandai, Kaito Hiroshi, 橋本総子, 大坪裕美, 石森真吾, Ninchoji Takeshi, Morisada Naoya, 中西浩一, 吉川徳茂, Iijima Kazumoto
    第47回日本小児腎臓病学会学術集会, Jun. 2012, Japanese, 東京, Domestic conference
    [Invited]
    Poster presentation

  • Gitelman症候群と偽性Gitelman症候群の臨床的差異に関する検討
    Ninchoji Takeshi, Kaito Hiroshi, 大坪裕美, 橋本総子, 石森真吾, 橋村裕也, Nozu Kandai, Morisada Naoya, Iijima Kazumoto
    第55回日本腎臓学会学術総会, Jun. 2012, Japanese, 横浜, Domestic conference
    [Invited]
    Poster presentation

  • 2q36-q37領域における部分母親性イソダイソミーによる常染色体劣性Alport症候群の1男性例
    橋本総子, 橋村裕也, 大坪裕美, 石森真吾, Ninchoji Takeshi, Kaito Hiroshi, Morisada Naoya, 高橋英彦, Nozu Kandai, Iijima Kazumoto
    第55回日本腎臓学会学術総会, Jun. 2012, Japanese, 横浜, Domestic conference
    [Invited]
    Poster presentation

  • 2q36-q37領域における部分母親性イソダイソミーによる常染色体劣性Alport症候群の1男性例
    橋本総子, 付 学軍, 橋村裕也, 大坪裕美, Ninchoji Takeshi, Kaito Hiroshi, Morisada Naoya, 高橋英彦, Nozu Kandai, Iijima Kazumoto
    第47回日本小児腎臓病学会学術集会, Jun. 2012, Japanese, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 巣状メキサンギウム増殖を示す小児IgA腎症に対するACEIの治療反応性
    島 友子, 中西 浩一, 濱 武継, 向山 弘展, 戸川 寛子, Nozu Kandai, 田中 亮二郎, Iijima Kazumoto, 吉川 徳茂
    第114回日本小児科学会学術集会, Aug. 2011, Japanese, 日本小児科学会, 東京, Domestic conference
    [Invited]
    Others

  • 小児IgA腎症におけるオックスフォード分類の有用性
    Ninchoji Takeshi, Kaito Hiroshi, 橋村 裕也, 神岡 一郎, Nozu Kandai, 中西 浩一, 田中 亮二郎, 吉川 徳茂, Iijima Kazumoto
    第54回日本腎臓学会学術総会, Jun. 2011, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Others

  • 血清アルブミン値と組織所見に基づいた小児紫斑病性腎炎の治療戦略
    Ninchoji Takeshi, Kaito Hiroshi, 橋村 裕也, 神岡 一郎, Nozu Kandai, 中西 浩一, 田中 亮二郎, 吉川 徳茂, Iijima Kazumoto
    第54回日本腎臓学会学術総会, Jun. 2011, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Others

  • Investigation of molecular background for patients with exercise-idcuced acute renal failure
    Kaito Hiroshi, Nozu Kandai, Nakanishi K, Hashimura Y, Shima Y, Ninchoji Takeshi, Yoshikawa N, Iijima Kazumoto, Matsuo M
    ERA-EDTA Congress, Jun. 2011, English, プラハ, チェコ, International conference
    [Invited]
    Others

  • Genotype-phenotype correlation of Japanese X-linked Alport syndrome.
    Hashimura Y, Nozu Kandai, Ishimori S, Otsubo H, Hashimoto S, Kaito Hiroshi, Nakanishi K, Yoshikawa N, Iijima Kazumoto, Matsuo M
    The 11th Asian Congress of Pediatric Nephrology, Jun. 2011, English, アジア小児腎臓学会, 福岡, International conference
    [Invited]
    Others

  • Deep intronic mutations in COL4A5 causes X-linked Alport syndrome.
    Hashimoto F, Nozu Kandai, Otsubo H, Ishimori S, Hashimura Y, Kaito Hiroshi, Nakanishi K, Yoshikawa N, Iijima Kazumoto, Matsuo M
    The 11th Asian Congress of Pediatric Nephrology, Jun. 2011, English, アジア小児腎臓学会, 福岡, International conference
    [Invited]
    Others

  • Compound heterozygous mutations in COL4A3 or COL4A4 may correlate with a better prognosis in autosomal-recessive Alport syndrome.
    Oka Masahiro, Iijima Kazumoto, Hashimura Y, Otsuka Y, Kaito Hiroshi, Nakanishi K, Yoshikawa N, Nozu Kandai, Matsuo M
    The 11th Asian Congress of Pediatric Nephrology, Jun. 2011, English, アジア小児腎臓学会, 福岡, International conference
    [Invited]
    Others

  • Clinical distinction between genetically-proven gitelman's and pseudo-gitelman's syndrome
    Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Hashimura Y, Nakanishi K, Yoshikawa N, Iijima Kazumoto, Matsuo M
    ERA-EDTA Congress, Jun. 2011, English, プラハ, チェコ, International conference
    [Invited]
    Others

  • Recurrent exercise-induced acute renal failure and PRES with severe renal hypouricemia by compound-heterozygous SLC2A9 mutation.
    Shima Y, Nozu Kandai, Togawa H, Kaito Hiroshi, Iijima Kazumoto, Matsuo M, Nakanishi K, Yoshikawa N
    Pediatric Academic Societies' 2011Annual Meeting, Apr. 2011, English, Pediatric Academic Societies, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • Alport syndrome associated with hemophilia A-molecular mechanism of phenotypic divergence between siblings.
    Hashimura Y, Nozu Kandai, Otsubo H, Hashimoto S, Ishimori S, Morisada Naoya, Kaito Hiroshi, Iijima Kazumoto, Matsuo M
    Pediatric Academic Societies' 2011Annual Meeting, Apr. 2011, English, Pediatric Academic Societies, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • The Relationship between Arginine Vasopressin Levels and Hyponatremia in Children Receiving Hypotonic or Isotonic Intravenous Fluids Following a Percutaneous Renal Biopsy
    Micchael L.Moritz, Nozu Kandai, Iijima Kazumoto
    Renal Week 2010, Nov. 2010, English, American Society of Nephrology 2010 Annual Meeting, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • Prognostic Factors in Childhood IgA Nephropathy with Focal Mesangial Proliferation Treated with Angiotensin Converting Enzyme Inhibitors
    島友子, 中西浩一, 戸川寛子, 向山弘展, 浜武継, Nozu Kandai, 田中亮二郎, Iijima Kazumoto, 吉川徳茂
    Renal Week 2010, Nov. 2010, English, American Society of Nephrology 2010 Annual Meeting, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • Epithelial-to-Mesenchymal Transition (EMT) in cpk Mouse, a Model of ARPKD
    戸川寛子, 中西浩一, 向山弘展, 浜武継, 島友子, 宮嶋正康, Nozu Kandai, 高橋久英, 長尾枝澄香, Iijima Kazumoto, 吉川徳茂
    Renal Week 2010, Nov. 2010, English, American Society of Nephrology 2010 Annual Meeting, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • Clinical and Immunohistochemical Analyses of Japanese Families with Genetically-Defined Autosomal-Recessive Alport Syndrome
    Iijima Kazumoto, 岡政史, 橋村裕也, 大塚泰史, Kaito Hiroshi, 佐渡義一, 楊 國昌, 中西浩一, 吉川徳茂, 永迫 博信, Nozu Kandai, 松尾雅文
    Renal Week 2010, Nov. 2010, English, American Society of Nephrology 2010 Annual Meeting, デンバー, アメリカ, International conference
    [Invited]
    Poster presentation

  • 幼少期発症のFibronectin腎症でFN1遺伝子に変異のあった1例
    川西智子, 笠原正登, 森潔, 横井 秀基, 桒原 孝成, 城 謙輔, 上杉憲子, 長田道夫, Nozu Kandai, Iijima Kazumoto, 向山 政志, 中尾 一和
    第40回日本腎臓学会西部学術大会, Oct. 2010, Japanese, 日本腎臓学会, 広島, アメリカ, Domestic conference
    [Invited]
    Oral presentation

  • Treatment Strategy and Outcome for Henoch-Schonlein Purpura Nephritis
    Ninchoji Takeshi, 橋村裕也, Kaito Hiroshi, Nozu Kandai, 神田杏子, 神岡一郎, 島友子, 濱平陽史, 中西浩一, 田中亮二郎, Iijima Kazumoto, 吉川徳茂, 松尾雅文
    the 15th Congress of the International Pediatric Nephrology Association, Aug. 2010, English, The International Pediatric Nephrology Association, ニューヨーク, アメリカ, International conference
    [Invited]
    Poster presentation

  • Natural Remission Rate and Prognostic Factors in Childhood IgANephropathy with Minimal Change or Focal Mesangial Proliferation
    島友子, 中西浩一, 戸川寛子, Nozu Kandai, 田中亮二郎, Iijima Kazumoto, 吉川徳茂
    the 15th Congress of the International Pediatric Nephrology Association, Aug. 2010, English, The International Pediatric Nephrology Association, ニューヨーク, アメリカ, International conference
    [Invited]
    Oral presentation

  • Clinical Characteristics of Genetically-Proven Gitelman's Syndrome
    Kaito Hiroshi, Nozu Kandai, 橋村裕也, 岡政史, Ninchoji Takeshi, 中西浩一, 吉川徳茂, Iijima Kazumoto, 松尾雅文
    the 15th Congress of the International Pediatric Nephrology Association, Aug. 2010, English, The International Pediatric Nephrology Association, ニューヨーク, アメリカ, International conference
    [Invited]
    Poster presentation

  • 微小変化・巣状メサンギウム増殖を示す小児IgA 腎症における自然寛解率とその予測因子
    島友子, 中西浩一, 戸川寛子, Nozu Kandai, 田中亮二郎, Iijima Kazumoto, 吉川徳茂
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 伴性優性遺伝の家族性良性血尿の1家系
    田中幸代, 蓮井正史, Nozu Kandai, Iijima Kazumoto, 杉本圭相, 竹村司, 金子一成
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 多嚢胞性異形成腎（MCDK）の兄弟例におけるHNF-1β 遺伝子変異
    蓮井正史, 磯崎夕佳, 田中幸代, 金子一成, Nozu Kandai, Iijima Kazumoto
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 常染色体劣性多発性嚢胞腎（ARPKD）モデルcpk マウスの尿細管上皮細胞における上皮間葉移行（EMT）
    戸川寛子, 中西浩一, 島友子, 佐古まゆみ, 向山弘展, 宮嶋正康, Nozu Kandai, 吉原大輔, 長尾枝澄香, Iijima Kazumoto, 吉川徳茂
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Poster presentation

  • 常染色体性Alport 症候群の臨床および分子生物学的検討
    岡政史, Nozu Kandai, Ninchoji Takeshi, 橋村裕也, Kaito Hiroshi, Iijima Kazumoto, 松尾雅文
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 運動後急性腎不全とPRESの合併を反復し、GLUT9遺伝子複合へテロ接合体変異を同定しえた腎性低尿酸血症の一例
    島友子, Nozu Kandai, 戸川寛子, Kaito Hiroshi, Iijima Kazumoto, 松尾雅文, 中西浩一, 吉川徳茂
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝子解析で確定診断しえたGitelman 症候群31例の臨床的検討
    Kaito Hiroshi, Nozu Kandai, 橋村裕也, 岡政史, Ninchoji Takeshi, Iijima Kazumoto, 松尾雅文
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Poster presentation

  • シクロスポリンにてネフローゼ症候群と食物アレルギー性腸炎の寛解維持が可能となったIPEX症候群の一例
    野田俊輔, 亀井宏一, 堤晶子, 宇田川智宏, 小椋雅夫, 伊藤秀一, 松岡健太郎, 金兼弘和, Nozu Kandai, Iijima Kazumoto
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • X染色体連鎖型Alport症候群と血友病Aを合併した一男児例―同胞男児間における表現型の差異についての分子遺伝学的検討―
    橋村裕也, Nozu Kandai, 岡政史, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto, 松尾雅文
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • LINE-1 レトロトランスポゾンの置換によるEYA1 遺伝子変異をともなったbranchio-oto-renal症候群の1女児例
    Morisada Naoya, Nozu Kandai, Nanna Dahl Rendtorff, 森下高弘, 宮川隆之, 松元透, LisbethTranebjaerg, Iijima Kazumoto, 松尾雅文, 楠原浩一
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • COL4A3/COL4A4 のヘテロ変異を有する菲薄基底膜症候群のドナーから腎移植を実施した2例
    梶保祐子, 水谷誠, 谷口貴実子, 上田博章, 古山政幸, 石塚喜世伸, 藤井寛, 近本裕子, 秋岡祐子, 岡政史, Nozu Kandai, Iijima Kazumoto, 服部元史
    第45回日本小児腎臓病学会学術集会, Jul. 2010, Japanese, 日本小児腎臓病学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • 平滑筋腫合併アルポート症候群（DL-AS)の遺伝学的検討
    岡政史, Nozu Kandai, Morisada Naoya, 平野大志, 藤永周一郎, Ninchoji Takeshi, 橋村裕也, Kaito Hiroshi, Iijima Kazumoto, 松尾雅文
    第53回日本腎臓学会学術総会, Jun. 2010, Japanese, 日本腎臓学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • 常染色体劣性遺伝を呈したAlport症候群の一例
    藤本陽子, 古野由美, 椛島成利, 中俣潤一, 坂東健一郎, 柴田達哉, 芹野良太, 岡政史, Iijima Kazumoto, Nozu Kandai, 田村 雅仁, 尾辻 豊
    第53回日本腎臓学会学術総会, Jun. 2010, Japanese, 日本腎臓学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • ヒトARPKDと相同遺伝子変異を有するPCK ratにおける上皮間葉移行
    戸川寛子, 中西浩一, 島友子, 佐古まゆみ, 向山弘展, 宮嶋正康, Nozu Kandai, 吉原大輔, 長尾枝澄香, Iijima Kazumoto, 吉川徳茂
    第53回日本腎臓学会学術総会, Jun. 2010, Japanese, 日本腎臓学会, 神戸, Domestic conference
    [Invited]
    Poster presentation

  • X染色体連鎖型Alport症候群の臨床的検討
    橋村裕也, Nozu Kandai, 岡政史, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto, 中西浩一, 吉川徳茂, 松尾雅文
    第53回日本腎臓学会学術総会, Jun. 2010, Japanese, 日本腎臓学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • 常染色体劣性Alport症候群女児例におけるIV型コラーゲンα1～α6鎖染色の検討
    三浦健一郎, 高橋和浩, 関根孝司, 柳澤敦広, 生井良幸, Nozu Kandai, 岡政史, Iijima Kazumoto, 内藤一郎, 五十嵐隆
    第113回日本小児科学会学術集会, Apr. 2010, Japanese, 日本小児科学会, 盛岡, Domestic conference
    [Invited]
    Oral presentation

  • レシピエント選定基準改定後に経験した小児献腎移植の5例
    Ninchoji Takeshi, 橋村裕也, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, 松尾雅文
    第113回日本小児科学会学術集会, Apr. 2010, Japanese, 日本小児科学会, 盛岡, Domestic conference
    [Invited]
    Oral presentation

  • 3歳健診から血尿と蛋白尿が持続し,Alport症候群の孤発例と考えられた女児例
    海野杏奈, 沢登恵美, 松下香子, 東田耕輔, 杉田完爾, Nozu Kandai, Krol Rafal P, Iijima Kazumoto
    第113回日本小児科学会学術集会, Apr. 2010, Japanese, 日本小児科学会, 盛岡, Domestic conference
    [Invited]
    Poster presentation

  • リツキシマブが著効した腎移植後重症EBウィルス感染症の一例
    橋村裕也, Kaito Hiroshi, Ninchoji Takeshi, Nozu Kandai, 兵頭洋二, Ishimura Takeshi, 竹田雅, 今留謙一, Fujisawa Masato, Iijima Kazumoto, 松尾雅文
    第43回日本臨床腎移植学会, Jan. 2010, Japanese, 日本臨床腎移植学会, 高知, Domestic conference
    [Invited]
    Oral presentation

  • 腎不全に至ったステロイド感受性微小変化型ネフローゼ症候群の１例
    Hashimura Yuya, Ninchoji Takeshi, Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    第39回日本腎臓学会西部学術大会, Oct. 2009, Japanese, 日本腎臓学会, 和歌山, Domestic conference
    [Invited]
    Oral presentation

  • 運動後急性腎不全とPRES(Posterior reversible encephalopathy syndrome)の合併を反復した腎性低尿酸血症の１例
    Nozu Kandai, Iijima Kazumoto
    第39回日本腎臓学会西部学術大会, Oct. 2009, Japanese, 日本腎臓学会, 和歌山, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝性腎疾患におけるintron内の変異に伴う病気発症メカニズム解明のための実験系の確立
    Nozu Kandai, Kaito Hiroshi, Hashimura Yuya, Ninchoji Takeshi, Iijima Kazumoto, Matsuo Masafumi
    第39回日本腎臓学会西部学術大会, Oct. 2009, Japanese, 日本腎臓学会, 和歌山, Domestic conference
    [Invited]
    Oral presentation

  • マイコプラズマ肺炎が関与したと考えられるアセトアミノフェンによる中毒性表皮壊死症の一例
    Oniki Shuntaro, Ikeda Tetsuya, Fukunaga Atsushi, Horikawa Tatsuya, Nishigori Chikako, Hashimura Yuya, Nozu Kandai, Taguchi Koji
    第60回日本皮膚科学会中部支部学術大会, Oct. 2009, Japanese, 日本皮膚科学会中部支部, 京都, Domestic conference
    [Invited]
    Poster presentation

  • Snail1 Is Involved in Epithelial-to-Mesenchymal Transition (EMT) in Cyst-Lining Epithelial Cells in PCK Rat
    Nozu Kandai, Iijima Kazumoto
    American Society of Nephrology 2009 Annual Meeting, Oct. 2009, English, American Society of Nephrology, サンディエゴ, アメリカ, International conference
    [Invited]
    Poster presentation

  • Investigation of Molecular Background for Patients with Exercise-Induced Acute Renal Failure
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    American Society of Nephrology 2009 Annual Meeting, Oct. 2009, English, American Society of Nephrology, サンディエゴ, アメリカ, International conference
    [Invited]
    Poster presentation

  • A Deep Intronic Mutation in the SLC12A3 Gene Leads to Gitelman Syndrome
    Nozu Kandai, Iijima Kazumoto, Kaito Hiroshi, Hashimura Yuya, Ninchoji Takeshi, Matsuo Masafumi
    American Society of Nephrology 2009 Annual Meeting, Oct. 2009, English, American Society of Nephrology, サンディエゴ, アメリカ, International conference
    [Invited]
    Poster presentation

  • 等張性輸液は手術後の低ナトリウム（Na）血症を防止する
    Hashimura Yuya, Kanda Kyoko, Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    第52回日本腎臓学会学術総会, Jun. 2009, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 小児ネフローゼ症候群患者におけるリツキシマブ血中濃度と投与後再発についての検討
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 重症小児IgA 腎症における治療反応性規定因子
    Nozu Kandai, Iijima Kazumoto
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 重症小児IgA腎症における治療後腎IgA沈着消失の臨床病理学的意義
    Nozu Kandai, Iijima Kazumoto
    第52回日本腎臓学会学術総会, Jun. 2009, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 遺伝性腎疾患におけるintron 内の変異に伴う病気発症メカニズム解明のためのin vivoおよびin vitro の実験系の確立
    Nozu Kandai, Kaito Hiroshi, Kanda Kyoko, Hashimura Yuya, Takeshima Yasuhiro, Iijima Kazumoto, Matsuo Masafumi
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • ヒトARPKD相同遺伝子ラットモデルにおける尿細管部位特異的嚢胞形成
    Nozu Kandai, Iijima Kazumoto
    第52回日本腎臓学会学術総会, Jun. 2009, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • X染色体連鎖型アルポート症候群（XLAS）の分子遺伝学的検討
    Nozu Kandai, Kaito Hiroshi, Kanda Kyoko, Hashimura Yuya, Iijima Kazumoto, Matsuo Masafumi
    第52回日本腎臓学会学術総会, Jun. 2009, Japanese, 日本腎臓学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • X 染色体連鎖型アルポート症候群の男性患者における糸球体基底膜４型コラーゲンα５鎖陽性例の検討
    Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    第44回日本小児腎臓病学会学術集会, Jun. 2009, English, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • NR３C２遺伝子変異に伴いmRNA にsplicing 異常を認めたにも関わらず軽症であった偽性低アルドステロン症１型の親子例
    Kanda Kyoko, Nozu Kandai, Hashimura Yuya, Miwa Akihiro, Morioka Ichiro, Yokoyama Naoki, Iijima Kazumoto, Matsuo Masafumi
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • IPEX 症候群に微小変化型ネフローゼ症候群を合併した１症例
    Hashimura Yuya, Nozu Kandai, Kanda Kyoko, Hayakawa Akira, Takeshima Yasuhiro, Iijima Kazumoto, Matsuo Masafumi
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • COL４A５遺伝子に９塩基の欠失を有し、GBM に４型コラーゲンα５鎖の正常の発現を認めたX 染色体連鎖型アルポート症候群男児例
    Nozu Kandai, Iijima Kazumoto
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • ARPKD 相同遺伝子ラットモデルの尿細管上皮細胞における上皮間葉移行（EMT）
    Nozu Kandai, Iijima Kazumoto
    第44回日本小児腎臓病学会学術集会, Jun. 2009, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • X染色体連鎖型アルポート症候群の分子遺伝学的検討
    Nozu Kandai, Kanda Kyoko, Hashimura Yuya, Iijima Kazumoto, Matsuo Masafumi
    第112回日本小児科学会学術集会, Apr. 2009, Japanese, 日本小児科学会, 奈良, Domestic conference
    [Invited]
    Oral presentation

  • リポソーバLA-15を用いた血漿吸着療法（LA-15PA）の検討－体重１９kgの小児に対するLDL-Aを経験して
    Abe Takaya, Fukagawa Masafumi, Nozu Kandai, Iijima Kazumoto
    第２９回日本アフェレシス学会学術大会, Nov. 2008, Japanese, 日本アフェレーシス学会, 広島, Domestic conference
    [Invited]
    Poster presentation

  • Treatment of Refractory Steroid-Dependent Nephrotic Syndrome with a Single Dose of Rituximab, a Multicenter Prospective Study.
    Nozu Kandai, Iijima Kazumoto
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • The First Case of Minimal Change Nephrotic Syndrome Associated with Immunodysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome.
    Hashimura Yuya, Nozu Kandai, Kanda Kyoko, Takeshima Yasuhiro, Hayakawa Akira, Iijima Kazumoto, Matsuo Masafumi
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Others

  • The first case of minimal change nephrotic syndrome associated with immunodysregulation, polyendocrinopathy, enteropathy, X-linked(IPEX) syndrome.
    Hashimura Yuya, Nozu Kandai, Kanda Kyoko, Takeshima Yasuhiro, Hayakawa Akira, Iijima Kazumoto, Matsuo Masafumi
    41th American Society of Pediatric Nephrology, Nov. 2008, English, 41th American Society of Pediatric Nephrology, フィラデルフィア, アメリカ, International conference
    [Invited]
    Oral presentation

  • TCF2 Mutation in Patients with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
    Nozu Kandai, Iijima Kazumoto
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • Somatic Mosaicism for a Mutation of the COL4A5 Gene in Three Sporadic X-Linked Alport Syndrome Cases.
    Nozu Kandai, Kaito Hiroshi, Kanda Kyoko, Hashimura Yuya, Iijima Kazumoto, Matsuo Masafumi
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • Somatic mosaicism for a mutation of the COL4A5 gene in three sporadic X-linked alport syndrome cases.
    Nozu Kandai, Kaito Hiroshi, Kanda Kyoko, Hashimura Yuya, Iijima Kazumoto, Matsuo Masafumi
    41th American Society of Pediatric Nephrology, Nov. 2008, English, 41th American Society of Pediatric Nephrology, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • Epithelial-to-Mesenchymal Transition in Cyst-Lining Epithelial Cells in PCK Rat.
    Nozu Kandai, Iijima Kazumoto
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • Elevated AVP Levels and Hyponatremia Following Percutaneous Renal Biopsies in Children.
    Iijima Kazumoto, Matsuo Masafumi, Kanda Kyoko, Nozu Kandai
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Poster presentation

  • Disappearance of Glomerular IgA Deposits in Severe Childhood IgA Nephropathy after 2-yr Combination/Prednisolone Therapy.
    Nozu Kandai, Iijima Kazumoto
    American Society of Nephrology 2008 Annual Meeting, Nov. 2008, English, tThai Pediatric Nephrology Association, フィラデルフィア, アメリカ, International conference
    [Invited]
    Others

  • 当院にて昨年1年間に経験した小児献腎移植の3例
    Hyodo Yoji, Ishimura Takeshi, Takeda Masashi, Kaito Hiroshi, Kanda Kyoko, Nozu Kandai, Miyake Hideaki, Tanaka Kazushi, Takenaka Atsushi, Iijima Kazumoto, Fujisawa Masato
    第30回日本小児腎不全学会, Oct. 2008, Japanese, 日本小児腎不全学会, 栃木, Domestic conference
    [Invited]
    Oral presentation

  • Molecular and clinical investigation for the X-linked alport syndrome.
    Nozu Kandai
    2008 the Korean Society of Pediatric Nephrology, Oct. 2008, English, Korean Society of Pediatric Nephrology, ソウル, 韓国, International conference
    [Invited]
    Oral presentation

  • アルポート症候群を原疾患とする慢性腎不全に対して施行された生体腎移植7例の検討
    Ishimura Takeshi, Hyodo Yoji, Nozu Kandai, Takeda Masashi, Miyake Hideaki, Tanaka Kazushi, Takenaka Atsushi, Fujisawa Masato
    第44回日本移植学会, Sep. 2008, Japanese, 日本移植学会, 大阪, Domestic conference
    [Invited]
    Oral presentation

  • III型Bartter症候群患者における利尿剤負荷試験～Gitelman症候群との類似性の機序に関する研究～
    Kanda Kyoko, Nozu Kandai, Kaito Hiroshi, Matsuo Masafumi, Iijima Kazumoto
    第43回日本小児腎臓病学会学術集会, Jun. 2008, Japanese, 日本小児腎臓学会, 福岡, Domestic conference
    [Invited]
    Oral presentation

  • Bartter症候群、Gitelman症候群の病型と臨床症状、遺伝学的背景に関する最近の知見
    Nozu Kandai
    第43回日本小児腎臓病学会学術集会, Jun. 2008, Japanese, 日本小児腎臓学会, 福岡, Domestic conference
    [Invited]
    Oral presentation

  • 小手術後の一過性血漿抗利尿ホルモン分泌亢進に関する研究
    Kanda Kyoko, Nozu Kandai, Kaito Hiroshi, Matsuo Masafumi, Iijima Kazumoto
    第51回日本腎臓学会学術総会, May 2008, Japanese, 日本腎臓学会, 福岡, Domestic conference
    [Invited]
    Oral presentation

  • Transient elevations of plasma antidiuretic hormone levels in children with post-operative nausea and vomiting after kidney biopsy.
    Kanda Kyoko, Nozu Kandai, Kaito Hiroshi, Hashimura Yuya, Iijima Kazumoto, Matsuo Masafumi
    Pediatric Academic Societies' 2008 Annual Meeting, May 2008, English, Pediatric Academic Societies, ハワイ, アメリカ, International conference
    [Invited]
    Poster presentation

  • 難治性全身性エリテマトーデス（SLE）に対してリツキシマブ(RTX)を投与した2症例
    Kanda Kyoko, Nozu Kandai, Kaito Hiroshi, Matsuo Masafumi
    第244回日本小児科会兵庫県地方会, Feb. 2008, Japanese, 日本小児科会兵庫県地方会, 西宮, Domestic conference
    Oral presentation

  • 全身性エリテマトーデスを合併した緩徐進行型1型糖尿病の1例
    Hiroyuki Awano, Yagi Mariko, Okizuka You, Kanda Kyoko, Kaito Hiroshi, Nozu Kandai, Takeshima Yasuhiro, Matsuo Masafumi
    第41回日本小児内分泌学会学術集会, Nov. 2007, Japanese, 日本小児内分泌学会, 横浜, Domestic conference
    [Invited]
    Poster presentation

  • 全身性エリテマトーデスを合併した緩徐進行型1型糖尿病の1例
    Hiroyuki Awano, Yagi Mariko, Okizuka You, Kanda Kyoko, Kaito Hiroshi, Nozu Kandai, Takeshima Yasuhiro, Matsuo Masafumi
    第41回小児内分泌学会学術集会, Nov. 2007, Japanese, 日本小児内分泌学会, 横浜, Domestic conference
    [Invited]
    Poster presentation

  • Molecular analysis of digenic inheritance in type IV Bartter syndrome phenotype .
    Nozu Kandai, Kaito Hiroshi, Iijima Kazumoto, Matsuo Masafumi
    TheAmericanSocietyofNephrologyRenalWeek2007, Oct. 2007, English, American Society of Nephrology, Calfornia, アメリカ, International conference
    [Invited]
    Poster presentation

  • Genetic backgrounds in patients with exercise-induced acute renal failure.
    Kaito Hiroshi, Nozu Kandai, Kanda Kyoko, Iijima Kazumoto, Matsuo Masafumi
    TheAmericanSocietyofNephrologyRenalWeek2007, Oct. 2007, English, American Society of Nephrology, Calfornia, アメリカ, International conference
    [Invited]
    Poster presentation

  • 末期腎不全に至り腎移植を行った小児ネフローゼ症候群4例の検討
    Kaito Hiroshi, Nozu Kandai, Kanda Kyoko, Iijima Kazumoto, Hyodo Yoji, Ishimura Takeshi, Takeda Masashi, Fujisawa Masato, Matsuo Masafumi
    第29回日本小児腎不全学会総会・学術集会, Sep. 2007, Japanese, 日本小児腎不全学会, 松江, Domestic conference
    [Invited]
    Oral presentation

  • 腎性低尿酸血症を伴わなかった運動後急性腎不全(ALPE)の1例
    Kaito Hiroshi, Nozu Kandai
    第29回日本小児腎不全学会総会・学術集会, Sep. 2007, Japanese, 日本小児腎不全学会, 松江, Domestic conference
    [Invited]
    Oral presentation

  • LDL吸着療法（LDL-A）が有効であった巣状分節性糸球体硬化症（FSGS）の一例
    Kaito Hiroshi, Nozu Kandai, Kanda Kyoko, Matsuo Masafumi
    第243回日本小児科学会兵庫県地方会, Sep. 2007, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference
    [Invited]
    Oral presentation

  • Transient elevation of plasma antidiuretic hormone level arter kindney biopsy associated with iatrogenic hyponatremia or postoperative nausea and vomit.
    Kanda Kyoko, Nozu Kandai, Iijima Kazumoto, Matsuo Masafumi
    14thCongressoftheInternationalPediatricNephrologyAssociation, Aug. 2007, English, International Pediatric Nephrology Association, Budapest, ハンガリー, International conference
    [Invited]
    Poster presentation

  • Molecular analysis of 5 Japanese patients with type III bartter syndrome.
    Nozu Kandai, Kanda Kyoko, Iijima Kazumoto, Matsuo Masafumi
    14thCongressoftheInternationalPediatricNephrologyAssociation, Aug. 2007, English, International Pediatric Nephrology Association, Budapest, ハンガリー, International conference
    [Invited]
    Poster presentation

  • Identification of 6 novel mutations in the COL4A5 gene of Japanese patients with X-linked alport syndrome.
    Nozu Kandai, Kanda Kyoko, Iijima Kazumoto, Matsuo Masafumi
    14thCongressoftheInternationalPediatricNephrologyAssociation, Aug. 2007, English, International Pediatric Nephrology Association, Budapest, ハンガリー, International conference
    [Invited]
    Poster presentation

  • 日本人3型Bartter症候群患者５例における遺伝子型および表現型に関する研究
    Nozu Kandai, Kaito Hiroshi, Kanda Kyoko, Iijima Kazumoto, Matsuo Masafumi
    第42回日本小児腎臓病学会学術集会, Jun. 2007, Japanese, 日本小児腎臓病学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 小手術後の一過性血漿抗利尿ホルモン分泌亢進に関する研究―医原性低ナトリウム血症および術後嘔気嘔吐症発症機序に関する考察―
    Kanda Kyoko, Nozu Kandai, Kaito Hiroshi, Matsuo Masafumi, Iijima Kazumoto
    第42回日本小児腎臓病学会学術集会, Jun. 2007, Japanese, 日本小児腎臓病学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 血清尿酸値の軽度低下を伴った運動後急性腎不全（ALPE）の２例―臨床的および遺伝学的検討―
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Kanda Kyoko, Matsuo Masafumi
    第42回日本小児腎臓病学会学術集会, Jun. 2007, Japanese, 日本小児腎臓病学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • 血管性紫斑病における腎炎発症とintercellular adhesion molecule-1 (ICAM-1)遺伝子多型K469Eの関与
    Nozu Kandai, Iijima Kazumoto
    第50回日本腎臓学会学術総会, May 2007, Japanese, 日本腎臓学会, 浜松, Domestic conference
    [Invited]
    Poster presentation

  • 運動後急性腎不全とURAT1遺伝子変異との関連についての検討
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Kanda Kyoko, Matsuo Masafumi
    第50回日本腎臓学会学術総会, May 2007, Japanese, 日本腎臓学会, 浜松, Domestic conference
    [Invited]
    Poster presentation

  • 運動後急性腎不全とURAT1遺伝子変異との関連についての検討
    Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Kanda Kyoko, Matsuo Masafumi
    第110回日本小児科学会学術集会, Apr. 2007, Japanese, 日本小児科学会, 京都, Domestic conference
    [Invited]
    Oral presentation

  • Alport症侯群に対する抗アルドステロン薬の効果についての検討
    KAITO HIROSHI, Nozu Kandai, MATSUO MASAFUMI
    第109回日本小児科学会学術集会, Apr. 2006, Japanese, 日本小児科学会学術集会事務局, 石川, Domestic conference
    [Invited]
    Oral presentation

  • 学校検尿で発見され、腎生検にてループス腎炎と診断された1例
    KAITO HIROSHI, Nozu Kandai, MATSUO MASAFUMI
    第238回 日本小児科学会兵庫県地方会, Feb. 2006, Japanese, 神戸大学 小児科, 兵庫, Domestic conference
    [Invited]
    Oral presentation

  • ステロイドパルス療法を要する重度の腹部症状を認めたHenoch-Schonlein紫斑病（HSP）の1例
    KAITO HIROSHI, Nozu Kandai, MATSUO MASAFUMI
    第238回 日本小児科学会兵庫県地方会, Feb. 2006, Japanese, 神戸大学 小児科, 兵庫, Domestic conference
    [Invited]
    Oral presentation

  • The national survey of typical hemolytic uremic syndrome in Japan: the analysis of the risk factors predicated the induction of dialysis and the development of central nervous system disorders
    Ichiro Kamioka, NOZU, kandai, Teruo Fujita, Kenichi Satomura, Kunihiko Yoshiya, IIJIMA,Kazumoto, Koichi Nakanishi, Norishige Yoshikawa, MATSUO, Masafumi
    American Society of Nephrology 38th Annual Renal Week Meeting, Nov. 2005, English, American Society of Nephrology, Philadelphia, International conference
    [Invited]
    Poster presentation

  • EYA1 and SIX1 gene mutations in Japanese patients with Branchio-Oto-Renal (BOR) syndrome and related diseases
    IIJIMA,Kazumoto, Okada M, NOZU, kandai, Okuyama T
    American Society of Nephrology 38th Annual Renal Week Meeting, Nov. 2005, English, American Society of Nephrology, Philadelphia, International conference
    [Invited]
    Poster presentation

  • 巣状分節性糸球体硬化症のフォロー中に発症したBasedow病の一例
    西山 敦史, 石橋 和人, 藤田 晃生, 神岡 一郎, NOZU, kandai, YAGI, Mariko, TAKESHIMA, Yasuhiro, MATSUO, Masafumi
    第39回日本小児内分泌学会, Oct. 2005, Japanese, 日本小児内分泌学会, 東京, Domestic conference
    [Invited]
    Poster presentation

  • Rituximabの投与がFSGSの移植後再発に対し有効であったと考えられた1例
    貝藤 裕史, NOZU, kandai, 神岡 一郎, 藤田 晃生, MATSUO, Masafumi, IIJIMA,Kazumoto, 吉川 徳茂, 兵頭 洋二, 石田 敏郎, TAKEDA, Masashi, FUJISAWA, Masato
    第277回日本小児腎不全学会, Sep. 2005, Japanese, 日本小児腎不全学会, 横浜, Domestic conference
    [Invited]
    Oral presentation

  • Factors involved in renal toxicity induced by cyclosporin A in pediatric patients with nephritic syndrome
    中村 任, NOZU, kandai, 加古 麻恵, 守屋 友加, 胡本 千穂, OKAMURA, Noboru, SAKAEDA, Toshiyuki, MATSUO, Masafumi, OKUMURA, Katsuhiko
    医療薬学フォーラム2005, Jul. 2005, Japanese, 日本薬学会, 鹿児島, Domestic conference
    [Invited]
    Poster presentation

  • 小児難治性ネフローゼ患者におけるシクロスポリンの腎毒性発現因子の解析
    中村 任, NOZU, kandai, 加古 麻恵, 守屋 友加, 胡本 千穂, OKAMURA, Noboru, SAKAEDA, Toshiyuki, MATSUO, Masafumi, OKUMURA, Katsuhiko
    医療薬学フォーラム2005／第13回クリニカルファーマシーシンポジウム, Jul. 2005, Japanese, 日本薬学会医療薬学部会, 鹿児島, Domestic conference
    [Invited]
    Poster presentation

  • 膜性増殖性糸球体腎炎（MPGN）24例の長期予後に関する検討
    藤田 晃生, 神岡 一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂, MATSUO, Masafumi
    第40回日本小児腎臓病学会, May 2005, Japanese, 日本小児腎臓病学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 全国調査における典型的溶血性尿毒症症候群の治療の検討
    神岡 一郎, NOZU, kandai, 藤田 晃生, 吉矢 邦彦, 里村 憲一, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川 徳茂, MATSUO, Masafumi
    第40回日本小児腎臓病学会, May 2005, Japanese, 日本小児腎臓病学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 小児難治性ネフローゼ患者におけるシクロスポリンの血中濃度推移と腎毒性の関係
    加古 麻恵, NOZU, kandai, 守屋 友加, 胡本 千穂, 中村 任, 大石 美惠, 西口 工司, SAKAEDA, Toshiyuki, MATSUO, Masafumi, OKUMURA, Katsuhiko
    第22回日本TDM学会学術大会, May 2005, Japanese, 日本TDM学会, 宜野座, Domestic conference
    [Invited]
    Oral presentation

  • Gene Scanを用いることで遺伝子異常を発見できた3型バーター症候群の1例
    NOZU, kandai, 付 学軍, NISHIO, Hisahide, 神岡 一郎, 藤田 晃生, 吉矢 邦彦, 郷司 克己, IIJIMA,Kazumoto
    第41回日本小児腎臓病学会, May 2005, Japanese, 日本小児腎臓病学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • Gene Scanを用いることで遺伝子異常を発見できた3型バーター症候群の1例
    NOZU, kandai, 付 学軍, NISHIO, Hisahide, 神岡 一郎, 藤田 晃生, 吉矢 邦彦, 郷司 克己, IIJIMA,Kazumoto
    第40回日本小児腎臓病学会, May 2005, Japanese, 日本小児腎臓病学会, 仙台, Domestic conference
    [Invited]
    Oral presentation

  • 当院における溶血性尿毒症症候群（HUS）の臨床的検討
    藤田 晃生, 神岡 一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂, MATSUO, Masafumi
    第108回日本小児科学会学術集会, Apr. 2005, Japanese, 日本小児科学会, 東京, Domestic conference
    [Invited]
    Poster presentation

  • 小児腎疾患患者におけるシクロスポリン体内動態に及ぼす併用薬・腎機能の影響
    西川 美香, 守屋 友加, 中村 任, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    日本薬剤学会第20年会, Mar. 2005, Japanese, 日本薬剤学会, 東京, Domestic conference
    [Invited]
    Poster presentation

  • Effects of coadministered drugs and renal function on cyclosporine disposition in pediatric patients with renal dysfunction
    西川 美香, 守屋 友加, 中村 任, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    日本薬剤学会第20回記念大会, Mar. 2005, Japanese, 日本薬剤学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 小児SLE患者に対する高用量ミゾリビン投与の試み
    NOZU, kandai, 神岡 一郎, 藤田 晃生, MATSUO, Masafumi
    第18回近畿小児科学会, Mar. 2005, Japanese, 近畿小児科学会, 京都, Domestic conference
    Oral presentation

  • 小児科領域におけるシクロスポリンの血中濃度推移と腎毒性との関係について
    加古 麻恵, NOZU, kandai, 守屋 友加, 胡本 千穂, 中村 任, 大石 美恵, 西口 工司, SAKAEDA, Toshiyuki, MATSUO, Masafumi, OKUMURA, Katsuhiko
    第26回日本病院薬剤師会近畿学術大会, Jan. 2005, Japanese, 日本病院薬剤師会近畿ブロック, 京都, Domestic conference
    [Invited]
    Poster presentation

  • 腎機能が保たれている時期に腹膜透析を導入した難治性ネフローゼ症候群の一例
    NOZU, kandai, 神岡 一郎, 藤田 晃生, 吉矢 邦彦, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川 徳茂, MATSUO, Masafumi
    第26回日本小児腎不全学会, Oct. 2004, Japanese, 日本小児腎不全学会, 長野, Domestic conference
    [Invited]
    Oral presentation

  • Mutatioral analysis of NKCC2, ROMK, CLCNKB and NCCT in 11 Japanese patients with clinically diagnosed Bartter syndrome.
    NOZU, kandai, Xa Jun Fu, Ichiro Kamioka, Teruo Fujita, Kunihiko Yoshiya, Katsumi Goji, Koichi Nakanishi, Norishige Yoshikawa, IIJIMA,Kazumoto, MATSUO, Masafumi
    American Society of Nephrology 37th Annual Meeting, Oct. 2004, English, American Society of Nephrology, St. Louis, International conference
    [Invited]
    Poster presentation

  • 小児患者におけるCycrosporineの体内動態とMDR1遺伝子多型の関連
    西川 美香, 山下 智美, 守屋 友加, 中村 任, YAGI, Mariko, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    第25回日本臨床薬理学会年会, Sep. 2004, Japanese, 日本臨床薬理学会, 静岡, Domestic conference
    [Invited]
    Poster presentation

  • 小児患者におけるCyclosprineの体内動態とMDR1遺伝子多型の関連性
    西川 美香, 山下 智美, 守屋 友加, 中村 任, YAGI, Mariko, OKAMURA, Noboru, SAKAEDA, Toshiyuki, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    第25回日本臨床薬理学会年会, Sep. 2004, Japanese, 日本臨床薬理学会, 静岡, Domestic conference
    [Invited]
    Poster presentation

  • 当院で経験したANCA関連血管炎症候群の2例の検討
    神岡 一郎, 藤田 晃生, NOZU, kandai, MATSUO, Masafumi, 浜平 陽史, TANAKA,Ryojiro, 北川 康作, IIJIMA,Kazumoto, 吉川 徳茂
    第39回日本小児腎臓病学会, Jul. 2004, Japanese, 日本小児腎臓病学会, 熊本, Domestic conference
    [Invited]
    Oral presentation

  • 巣状膜性糸球体腎炎（FMGN）-びまん性膜性糸球体腎炎（DMGN）との比較検討-
    尾鼻 美奈, 中西 浩一, 佐古 まゆみ, 矢田 菜穂子, NOZU, kandai, TANAKA,Ryojiro, IIJIMA,Kazumoto, 吉川 徳茂
    第39回日本小児腎臓病学会, Jul. 2004, Japanese, 日本小児腎臓病学会, 熊本, Domestic conference
    [Invited]
    Oral presentation

  • Rituximab の投与が、FSGSの移植後再発に対し有効であったと考えられた１例-FSGSとBリンパ球活性化の関与に関する考察-
    NOZU, kandai, 神岡 一郎, 藤田 晃生, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂
    第39回日本小児腎臓病学会, Jul. 2004, Japanese, 日本小児腎臓病学会, 熊本, Domestic conference
    [Invited]
    Oral presentation

  • Bartter症候群８例における遺伝子解析
    付 学軍, NOZU, kandai, 神岡 一郎, 藤田 晃生, MATSUO, Masafumi, 吉矢 邦彦, 宮下 律子, 島 雅昭, 中島 敏博, 中西 浩一, 吉川 徳茂, IIJIMA,Kazumoto
    第39回日本小児腎臓病学会, Jul. 2004, Japanese, 日本小児腎臓病学会, 熊本, Domestic conference
    [Invited]
    Oral presentation

  • Mutations in the anion exchanger 1 (AE1) gene cause Southeast Asian ovalocytosis (SAO) and distal renal tubular acidosis (dRTA)
    神岡 一郎, NOZU, kandai, YM ナラザ, HV ロステンベルゲ, NISHIO, Hisahide, MATSUO, Masafumi
    第23回臨床細胞分子遺伝研究会, Jun. 2004, Japanese, 臨床細胞分子遺伝研究会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • C2 monitoring of cyclosporine in pediatric patients
    Yuka Moriya, Tsutomu Nakamura, SAKAEDA, Toshiyuki, NOZU, kandai, TANAKA,Ryojiro, IIJIMA,Kazumoto, MATSUO, Masafumi, OKUMURA, Katsuhiko
    2nd Pharmaceutical sciences world congress, Jun. 2004, English, 京都, International conference
    [Invited]
    Poster presentation

  • Association of genetic polymorphism at positions 2677 and 3435 of MDR1 gene with pharmacokinetics of cyclosporine in Japanese pediatric patients
    Tsutomu Nakamura, SAKAEDA, Toshiyuki, Yuka Moriya, Atsushi Wada, NOZU, kandai, MATSUO, Masafumi, OKUMURA, Katsuhiko
    2nd Pharmaceutical sciences world congress, Jun. 2004, English, 京都, International conference
    [Invited]
    Poster presentation

  • 日本人家族性巣状分節性糸球体硬化症におけるαアクチニン4遺伝子とポドシン遺伝子変異の検索
    佐古 まゆみ, 中西 浩一, 矢田 菜穂子, 尾鼻 美奈, NOZU, kandai, TANAKA,Ryojiro, IIJIMA,Kazumoto, 池田 昌弘, 本田 雅敬, 吉川 徳茂
    第47回日本腎臓学会学術総会, May 2004, Japanese, 日本腎臓学会, 栃木, Domestic conference
    [Invited]
    Oral presentation

  • 当院における典型的MPGNおよびAtypical MPGNの臨床的検討
    藤田 晃生, 神岡 一郎, NOZU, kandai, TANAKA,Ryojiro, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂, MATSUO, Masafumi
    第47回日本腎臓学会学術総会, May 2004, Japanese, 日本腎臓学会, 栃木, Domestic conference
    [Invited]
    Poster presentation

  • 非典型的膜性増殖性糸球体腎炎(Atypical MPGN)の臨床的検討
    藤田 晃生, 神岡 一郎, NOZU, kandai, 吉川 徳茂, MATSUO, Masafumi
    第107回日本小児科学会, Apr. 2004, Japanese, 日本小児科学会, 岡山, Domestic conference
    [Invited]
    Poster presentation

  • 小児患者におけるシクロスポリンC2モニタリングに関する検討
    守屋 友加, 和田 敦, 中村 任, SAKAEDA, Toshiyuki, 西口 工司, 西庄 京子, NOZU, kandai, TANAKA,Ryojiro, IIJIMA,Kazumoto, OKUMURA, Katsuhiko
    第13回医療薬学会年会, Sep. 2003, Japanese, 日本医療薬学会, 神戸, Domestic conference
    [Invited]
    Oral presentation

  • キャンピロバクター腸炎後に溶血性尿毒症症候群を発症し末期腎不全へと至った7歳女児例
    神岡 一郎, NOZU, kandai, MATSUO, Masafumi, 石田 敏郎, TAKEDA, Masashi, TANAKA,Ryojiro, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂
    第25回日本小児腎不全学会, Sep. 2003, Japanese, 日本小児腎不全学会, 群馬, Domestic conference
    [Invited]
    Oral presentation

  • Blood access確保に難渋した、維持血液透析を余儀なくされた2歳女児例
    NOZU, kandai, 神岡 一郎, 藤田 晃生, MATSUO, Masafumi, MAEDA, Kousaku, FUKAGAWA, Masafumi, TANAKA,Ryojiro, 吉矢 邦彦, IIJIMA,Kazumoto
    第25回日本小児腎不全学会, Sep. 2003, Japanese, 日本小児腎不全学会, 群馬, Domestic conference
    [Invited]
    Oral presentation

  • 非典型的な経過をとり腎生検を施行した溶血性尿毒症症候群についての検討
    神岡 一郎, NOZU, kandai, TANAKA,Ryojiro, NAKAMURA,Hajime, MATSUO, Masafumi, 吉矢 邦彦, IIJIMA,Kazumoto, 吉川 徳茂
    第38回日本小児腎臓病学会学術集会, Jul. 2003, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 小児科におけるネオーラル薬物動態に関する研究
    NOZU, kandai, 神岡 一郎, TANAKA,Ryojiro, MATSUO, Masafumi, 和田 敦, 喜多 知子, SAKAEDA, Toshiyuki, OKUMURA, Katsuhiko, 本田 雅敬, 池田 昌弘, IIJIMA,Kazumoto
    第38回日本小児腎臓病学会学術集会, Jul. 2003, Japanese, 日本小児腎臓病学会, 東京, Domestic conference
    [Invited]
    Oral presentation

  • 小児におけるネオーラル薬物動態に関する研究
    NOZU, kandai, 神岡 一郎, SAKAEDA, Toshiyuki, 喜多 知子, 和田 敦, OKUMURA, Katsuhiko, TANAKA,Ryojiro, NAKAMURA,Hajime, MATSUO, Masafumi, 本田 雅敬, 池田 昌弘, IIJIMA,Kazumoto
    第46回日本腎臓学会学術集会, May 2003, Japanese, 日本腎臓学会, 東京, Domestic conference
    Poster presentation

  • 小児科におけるネオーラル薬物動態に関する研究
    NOZU, kandai, 神岡 一郎, TANAKA,Ryojiro, NAKAMURA,Hajime, MATSUO, Masafumi, 本田 雅敬, 池田 昌弘, IIJIMA,Kazumoto
    第106回日本小児科学会学術集会, Apr. 2003, Japanese, 日本小児科学会, 福岡, Domestic conference
    [Invited]
    Oral presentation

■ Research Themes
  • OCRL異常の病態解明とLowe症候群に対する酵素補充療法の開発
    榊原 菜々, 薗田 啓之, 野津 寛大
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026

  • Contribution of aberrant splicing to the onset mechanisms in inherited kidney diseases
    野津 寛大
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

  • レニンアンギオテンシン系に着目した早産、低出生体重児の腎障害進展機序の解明研究
    石森 真吾, 堀之内 智子, 野津 寛大
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 社会医療法人愛仁会高槻病院(臨床研究センター), 01 Apr. 2023 - 31 Mar. 2026

  • Elucidation of the mechanism of rituximab-induced long-term remission in childhood nephrotic syndrome
    飯島 一誠, 堀之内 智子, 野津 寛大, 宮西 正憲
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

  • Elucidation of the mechanism of rituximab-induced long-term remission in childhood nephrotic syndrome
    飯島 一誠, 堀之内 智子, 野津 寛大, 宮西 正憲
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

  • Joint international Research Project for International GWAS Meta-Analysis and Anti-Nephrin Autoantibodies in Childhood Nephrotic Syndrome
    飯島 一誠, 賈 暁媛, 堀之内 智子, 長野 智那, 野津 寛大
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Kobe University, 07 Oct. 2021 - 31 Mar. 2024
    本研究は、Boston Children’s Hospital-HarvardのMatthew Sampson博士との国際共同研究であり、①国際GWASメタ解析で明らかになった7つの新たな疾患感受性遺伝子候補領域から疾患感受性遺伝子を同定すること、②日本人小児NS患者の病因として抗ネフリン自己抗体がどの程度関与しているのか、どのようなメカニズムでネフリンに対する自己免疫が生じるのかを疾患感受性遺伝子の側面から解明することを目的とする。 令和3年度は、日本人若手研究分担者である長野が、2021年6月より、Sampson博士の研究室で、研究を開始し、7つの疾患感受性遺伝子候補領域のfine-mappingを実施し、Nephrotic Syndrome Study Network (NEPTUNE)が保有する特発性ネフローゼ症候群患者の全ゲノム情報と腎生検検体（腎糸球体及び尿細管）のRNA-Seq情報を統合したデータベース（NephQTL）や、Harvard大学が保有する免疫細胞RNA-Seqデータベースとの統合解析を実施し、それぞれの遺伝子の発現パターンを明らかにした。一方、神戸大学を中心とした日本側の研究者は、小児特発性ネフローゼ症候群患者15例の活動期（高度蛋白尿出現時）と寛解期（蛋白尿消失期）のペア血漿を収集し、そのサンプルをBoston Children’s Hospitalに送った。現在、その結果を待っているところである。

  • Clarification of the pathogenesis of childhood nephrotic syndrome using iPS cell-derived kidney organoids
    Iijima Kazumoto
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2020 - 31 Mar. 2023
    From 11 Japanese pediatric patients with nephrotic syndrome, we generated iPS cells with null (n = 5), hetero (n = 4) or homo (n = 2) risk haplotypes of the gene NPHS1 that encodes Nephrin, the most important slit-membrane major component protein as a urinary protein prevention mechanism. They also succeeded in producing kidney organoids from some of the iPS cells. In the future, all iPS cells will be induced to differentiate into kidney organoids or renal glomerular podocytes to clarify the relationship between NPHS1 risk haplotype and NPHS1 gene expression.

  • Contribution of aberrant splicing to the onset mechanisms in inherited kidney diseases
    Kandai Nozu
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022
    We have investigated in vitro, in vivo, and clinical viewpoints that splicing abnormalities in the pathogenesis mechanism and severity of various hereditary renal diseases are greatly involved. As a result, the substitution of the last base of the exon, which has been interpreted as a missense variant, causes a splicing abnormality, and as a result, the analysis of the genotype-phenotype correlation has been conducted based on incorrect information. It was also clarified that some hereditary renal diseases can be treated by controlling splicing. We have succeeded in finding a lot of important information that will lead to the development of therapeutic methods using nucleic acid drugs.

  • Alport症候群に対するエクソンスキッピング療法の開発
    国立研究開発法人日本医療研究開発機構 戦略推進部 難病研究課, 難治性疾患実用化研究事業Step1, 神戸大学, Apr. 2020 - Mar. 2022, Principal investigator

  • Joint International Research for identification of disease-susceptible genes and drug-sensitive genes in childhood nephrotic syndrome
    IIJIMA KAZUMOTO
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Kobe University, 09 Oct. 2018 - 31 Mar. 2021
    To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (Pmeta=6.71E-28, OR=1.88) and TNFSF15 (Pmeta=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4).

  • Identification of Genes Involved in the Severity of Alport Syndrome and Elucidation of the Mechanism of its Severity
    Iijima Kazumoto
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2017 - 31 Mar. 2020
    It was confirmed that there was no correlation in clinical feature and genotype in the X-linked Alport syndrome (XLAS) female patients. Furthermore, since no disease-modifying gene mutations were identified in most severely ill patients, the severity of female XLAS patients was considered to be multifactorial. Molecular simulation analysis of the α3,4,5 (IV) chain revealed that when the exon with the stop codon was skipped, the α3,4,5 (IV) chain with COL4A5 truncating mutations showed three-dimensional structure similar to that of the normal α3,4,5 (IV) chain. These results strongly suggest that the modification of the truncating mutation to the non-truncating mutation by exon skipping therapy may attenuate XLAS. We also found that the severity of patients with COL4A5 missense mutations was correlated to the ability of the α3,4,5 (IV) chain to form trimers.

  • Alport症候群に対する新規治療法の開発
    NOZU Kandai
    AMED, AMED, Apr. 2017 - Mar. 2020, Principal investigator
    Competitive research funding

  • Verification of ADPKD's Two-hit theory using next-generation sequencer
    Fujimura Junya, Iijima Kadumoto, Nozu Kandai
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2017 - 31 Mar. 2019
    We investigated and elucidated two-hit theory using blood samples and isolated kidneys of patients for the purpose of elucidation of the pathophysiology of autosomal dominant poly cystic kidney disease (ADPKD), and finally from the findings The research was conducted in order to find out the possibility of new treatment. Analysis with NGS of the case where consent was obtained and direct confirmation with Sanger method were performed. In order to improve the search efficiency of screening, we are trying to create a disease panel specialized for PKD1 and PKD2 genes. We did examining DNA extracted from patient's blood-derived DNA as well as DNA extracted from cystic epithelial cells of the kidney, which were isolated from the patient, and refer to the past literature for techniques for establishing cultured cells using tissue fragments from the isolated kidney established and standardized the procedure.

  • Establishment of a comprehensive diagnostic method using next generation sequencer for Alport syndrome
    Yamamura Tomohiko, IIJIMA Kazumoto, NOZU Kandai, MINAMIKAWA Shogo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2018
    We established a diagnostic system that comprehensively analyze podocyte-related 45 genes by targeted sequencing using next generation sequencer (NGS). We analyzed 185 families suspected as having Alport syndrome (AS) and causative variants were identified in 147 families. As a result of large-scale analysis, it was possible to analyze the genotype-phenotype correlation of AS and we reported on the details about female patients with X-linked AS. We also clarified that NGS analysis detects other inherited kidney diseases, AS patients with copy number variation or somatic mosaic.

  • Nozu Kandai
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2015 - Mar. 2018, Principal investigator
    We established a comprehensive diagnostic system for inherited salt-losing tubulopathies by targeted sequencing. As a result, we have performed genetic diagnosis of approximately 150 cases in three years, and now we have received analysis requests of 5-10 samples monthly. As a result, 1. Established the methodologies for Identification of deep intronic mutations in Gitelman syndrome, and for pathogenicity search of intra-intron mutations, 2. Established the novel methodology for detecting Copy Number Variation and identified HNF1B deletion which was causative variant for pseudo-Bartter syndrome. 3. We clarified the mechanism of the development of pseudo - Barter syndrome in hereditary hypercalcemic hypocalcemia.
    Competitive research funding

  • Iijima Kazumoto, Syono Akemi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, Apr. 2014 - Mar. 2017
    The purpose of this study is to prove the basic concept of the exon-skipping therapy, a molecular therapy, for male patients with X-linked Alport syndrome, the most popular hereditary nephritis with poor prognosis. The exon-skipping by antisense oligonucleotides will convert severe mutations to milder ones. In this study, we found that antisense oligonucleotides actually induced the exon-skipping in cultured cells obtained from patients and in model mice having the same mutation in the patient. We will apply this therapy to patients with Alport syndrome in the future.
    Competitive research funding

  • The investigation for mechanism of tubular injury with diarrhea associated hemolytic uremic syndrome
    Takeshi Ninchoji, IIJIMA Kazumoto
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2013 - 31 Mar. 2016
    The purpose of this study is to reveal the mechanism of tubular injury with diarrhea associated hemolytic uremic syndrome (D+HUS). At first, we gave Shiga toxin (ST) 1, and 2 to human tubular cultured cell to examine the maximal concentration and duration of toxin. As the result, 10*-7 in 24 hours of ST was most suitable condition with maximal apoptosis. Second, messenger RNA of apoptosis related protein was analyzed with array PCR method. However, few significant factors of apoptosis was not identified with the definite pathway of apoptosis. Same results was found in serum of patients with D+HUS. Third, we examine cytokines which developed during tubular injury. In our assay, there were no significant cytokines. Thus, our strategy or our assay were difficult to reveal tubular injury.

  • KANDAI Nozu, IIJIMA Kazumoto, SHONO Akemi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Research Activity Start-up, Kobe University, Aug. 2013 - Mar. 2015, Principal investigator
    1. We conducted the genetic analysis for 250 suspected Alport syndrome family members and conducted the genotype-phenotype analysis. 2.From patients urine samples, we collected the urinary sediment cells and cultured those cells, and made the disease specific cell lines for the further experiment. 3.We conducted the immunohistochemical analysis of type IV collagen alpha 5 chain (a5) expression and identified that patients with truncating mutations don't express a5, on the contrary, patients with non-truncating mutations express a5. 4. We designed the antisense-oligonucleotide and tried to lead to exon skipping for some of the specific exons. One of them introduced the exon skipping and possibly lead truncating mutations to non-truncating mutations.
    Competitive research funding

  • 野津 寛大
    日本学術振興会, 科学研究費補助金／若手研究(B), 若手研究(B), 神戸大学, 2009 - 2010, Principal investigator
    先天性尿細管チャネル・輸送体異常症として発症頻度の高い、Bartter症候群、Gitelman症候群、偽性低アルドステロン症に関する最新の解析技術を用い、良好な結果を得たので報告を行った。 1, Bartter症候群・Gitelman症候群:それぞれの病気において、遺伝子解析における変異検出率は決して高くないことが知られているが、私たちは、従来のゲノムDNAからのPCRおよび直接シークエンス法に加え、尿中落下細胞から抽出したmRNAを用いたRT-PCR法やPCR半定量による広範囲ヘテロ接合体欠失の同定など、最新の遺伝子解析技術を駆使することで、その変異検出率を大幅に向上させることに成功した(Nozu Pediat Research 2009, Nozu Hum Genet 2009)。 2, 偽性低アルドステロン症:同疾患は新生児期に高カリウム血症、体重増加不良を認めるものの自然軽快する疾患である。更に本疾患は常染色体優性遺伝形式をとる疾患であるが、その発症機序は変異のあるalleleが産生するタンパクによるdominant negative効果により発症するか、一つのalleleに変異があるためMR受容体産生量が減少することによるhaplo insufficiency効果により発症するのか未だに不明である。私たちは従来の解析方法でMR遺伝子に新規の変異を同定し、さらに尿中落下細胞から抽出したmRNAを用いたsplicing異常の同定により、dominant negative効果により発症する機序が否定できないことを証明した(Kanda, Nozu BMC Nephrol 2009)。
    Competitive research funding

  • Identification of novel genes for congenital anomalies of Kidney and urinary tract (CAKUT) by CNV analyses and development of comprehensive gene testing for CAKUT
    IIJIMA Kazumoto, NAGATA Michio, NAKAYAMA Makioko, MORISADA Naoya, NOZU Kandai, HASHIMURA Yuya
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 2008 - 2010
    Copy number variation (CNV) of human genome is associated with several diseases including congenital anomalies. To identify new genes responsible for congenital anomalies of kidney and urinary tract (CAKUT), we utilized Agilent genome-wide CNV 400k array. We identified 4 CNV regions, which were not detected in healthy controls and CNV databases. We found 8 genes within or around these CNV regions. Of these genes, we identified a gene in which a CAKUT-specific heterozygous deletion resulted in deletion of 3 exons. We will analyze whether these genes are responsible for CAKUT. We developed comprehensive gene testing systems for known CAKUT genes (HNF1B, PAX2, EYA1, SIX1, SALL1) using multiplex ligation-dependent probe amplification and mRNA level analysis as well as direct sequencing of genomic DNA.

  • NOZU Kandai
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe University, 2007 - 2008, Principal investigator
    Bartter症候群(BS)、Gitelman症候群(GS)は常染色体劣性尿細管機能異常症で、低カリウム血症、代謝性アルカローシス、高レニン、高アルドステロン血症などを特徴とする。日本人におけるこれらの疾患を有する患者において、臨床的および遺伝学的検討はこれまで行われてこなかったが、私たちは今回の研究で、現在までに53例で遺伝子解析による確定診断を行ってきた。その結果、典型例ではそのほとんどで遺伝子変異を同定することができ、本疾患においては遺伝子診断率が高い疾患であることが分かった。また、解析方法に関する工夫を行い、尿中落下細胞からmRNAを抽出し、RT-PCRを用いて解析を行うという非侵襲的かつ斬新な方法を導入することで、遺伝子診断率を向上させることに成功し、さらに、これまでこれらの疾患で遺伝子診断率が低かった原因として、従来の直接シークエンス法による解析では広範囲のヘテロ接合体欠失の検出はできず、BS患者においてはこの変異が多いためであることを明らかにした。そこで、PCR半定量法を導入することで、それらの変異の検出に成功した。現在まで私たちは90%以上の患者において遺伝子変異の検出に成功した。
    Competitive research funding

  • 野津 寛大
    日本学術振興会, 科学研究費補助金／若手研究(B), 若手研究(B), 神戸大学, 2005 - 2006, Principal investigator
    Bartter症候群(BS)、Gitelaman症候群(GS)は常染色体劣性遺伝性尿細管機能異常症で、低カリウム血症,代謝性アルカローシス、高レニン、高アルドステロン血症を認めるにも関わらず正常血圧を示すことなどを特徴とする。現在までにI型からV型BSおよびGSの責任遺伝子が明らかとされている。 日本人におけるこれらの疾患を有する患者において、臨床的および遺伝学的検討はこれまで行われてこなかったが、私たちは今回の研究で、BSではI型9名、II型2名、III型5名、IV型1名、GSでは11名の患者において、その遺伝子異常を明らかとしている。また、解析方法に関する工夫を行い、尿中落下細胞からmRNAを抽出し、RT-PCRを用いて解析を行うという非侵襲的かつ斬新な方法を導入することで、遺伝子診断率を向上させることに成功し、英文学術誌に投稿を行った(Pediatric Research in press)。さらに、これまでこれらの疾患で遺伝子診断率が低かった原因として、従来の直接シークエンス法による解析では広範囲のヘテロ接合体欠失の検出はできず、BS患者においてはこの変異が多いためであることを明らかにした。そこで、PCR半定量法を導入することで、それらの変異の検出に成功した(現在投稿中)。また、日本人においては2型BSの報告例はこれまで1例もなかったが、2型BSでは低カリウム血症を認めない症例もいることを明らかとし、診断がついていない症例の存在の可能性を明らかとした(Pediatric Nephrology in press)。現在まで私たちは90%以上の患者において遺伝子変異の検出に成功している。更なる症例の蓄積を行い、日本人におけるこれらの疾患の患者の特徴を明らかとしていく予定である。
    Competitive research funding

  • Molecular epidemiology of neonatal Gilbert's syndrome in Malaysia
    NISHIO Hisahide, MATSUO Masafumi, TAKASIMA Yasuhiro, YOKOYAMA Naoki, NISHIYAMA Kaoru, SIRAKAWA Taku
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 2003 - 2004
    1 (Purpose) To clarify whether the UGT1A1 mutations contribute to the high incidence of neonatal jaundice in Southeast Asian populations, we screened for the mutations in the Malay-Malaysian populations. A total of 105 Malay-Malaysian newborn infants were enrolled in this study : 55 with jaundice and 50 without jaundice (non-jaundice). We used denaturing high-performance liquid chromatography (DHPLC) to detect the mutations, and GeneScan analysis to determine the TA-repeat number of the TATA box. 2 (G71R mutation) In the jaundice group, the genotype distribution for G71R mutation was as follows : 52 G/G, three G/R and no R/R infants, and the mutated allele frequency was 0.027. In the non-jaundice group, genotype distribution for the mutation was as follows : 47 G/G, three G/R and no R/R infants, and the mutated allele frequency was 0.030. 3 (G493R mutation) In the jaundice group, the genotype distribution for G493R mutation was as follows : 50 G/G, one G/R and no R/R infants, and the mutated allele frequency was 0.009. In the non-jaundice group, genotype distribution for the mutation was as follows : 50 G/G, no G/R and no R/R infants, and the mutated allele frequency was 0.000. 4 (variant TATA box) In the jaundice group, the genotype distribution for TA-7 variant was as follows : 41 TA-6/TA-6, ten TA-6/TA-7 and four TA-7/TA-7 infants, and the mutated allele frequency was 0.16. In the non-jaundice group, genotype distribution for the mutation was as follows : 43 TA-6/TA-6, six TA-6/TA-7 and one TA-7/TA-7 infants, and the mutated allele frequency was 0.08. 5 (Conclusion) The UGT1A1 mutations were not rare in Malay-Malaysian infants (〜30%), indicating the high incidence of Gilbert syndrome in the Malaysian population. The UGT1A1 mutations, especially variant TATA-box, were found more frequently in the jaundice group, suggesting that they are risk factors for the development of neonatal jaundice.

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