Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology
Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in ad...
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Elsevier
2024-04-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924000378 |
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| author | Takuya Fujimaru Takayasu Mori Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Fumiaki Ando Yutaro Mori Koichiro Susa Yuta Nakano Takao Shoji Yuichiro Fukudome Naoto Inaba Kenichiro Kitamura Taichi Nakanishi Keiko Uchida Toshihiro Kimura Teiichi Tamura Kiyoshi Ozawa Shinichi Uchida Eisei Sohara |
| author_facet | Takuya Fujimaru Takayasu Mori Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Fumiaki Ando Yutaro Mori Koichiro Susa Yuta Nakano Takao Shoji Yuichiro Fukudome Naoto Inaba Kenichiro Kitamura Taichi Nakanishi Keiko Uchida Toshihiro Kimura Teiichi Tamura Kiyoshi Ozawa Shinichi Uchida Eisei Sohara |
| author_sort | Takuya Fujimaru |
| collection | DOAJ |
| description | Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. Methods: This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Results: Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases. |
| format | Article |
| id | doaj-art-b98057d8afb84ca6a848b3c337e69b45 |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-b98057d8afb84ca6a848b3c337e69b452025-08-20T03:45:07ZengElsevierKidney International Reports2468-02492024-04-0194994100410.1016/j.ekir.2024.01.027Genetic Diagnosis of Adult Hemodialysis Patients With Unknown EtiologyTakuya Fujimaru0Takayasu Mori1Motoko Chiga2Shintaro Mandai3Hiroaki Kikuchi4Fumiaki Ando5Yutaro Mori6Koichiro Susa7Yuta Nakano8Takao Shoji9Yuichiro Fukudome10Naoto Inaba11Kenichiro Kitamura12Taichi Nakanishi13Keiko Uchida14Toshihiro Kimura15Teiichi Tamura16Kiyoshi Ozawa17Shinichi Uchida18Eisei Sohara19Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Correspondence: Eisei Sohara or Takayasu Mori, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.Clinical Laboratory, Tokyo Medical and Dental University (TMDU) Hospital, Tokyo JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanMiura Seaside Clinic, Miura, JapanZushi Sakurayama Clinic, Zushi, JapanKitakurihama Takuchi Clinic, Yokosuka, JapanKitakurihama Takuchi Clinic, Yokosuka, JapanKitakurihama Takuchi Clinic, Yokosuka, JapanYokosuka Clinic, Yokosuka, JapanYokosuka Clinic, Yokosuka, JapanYokosuka Clinic, Yokosuka, JapanYokosuka Clinic, Yokosuka, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Correspondence: Eisei Sohara or Takayasu Mori, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. Methods: This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Results: Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.http://www.sciencedirect.com/science/article/pii/S2468024924000378chronic kidney diseasegenetic analysishemodialysisinherited kidney disease |
| spellingShingle | Takuya Fujimaru Takayasu Mori Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Fumiaki Ando Yutaro Mori Koichiro Susa Yuta Nakano Takao Shoji Yuichiro Fukudome Naoto Inaba Kenichiro Kitamura Taichi Nakanishi Keiko Uchida Toshihiro Kimura Teiichi Tamura Kiyoshi Ozawa Shinichi Uchida Eisei Sohara Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology Kidney International Reports chronic kidney disease genetic analysis hemodialysis inherited kidney disease |
| title | Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology |
| title_full | Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology |
| title_fullStr | Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology |
| title_full_unstemmed | Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology |
| title_short | Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology |
| title_sort | genetic diagnosis of adult hemodialysis patients with unknown etiology |
| topic | chronic kidney disease genetic analysis hemodialysis inherited kidney disease |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924000378 |
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