Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2024 May 20

PMID 38765603

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 pathogenic variants, and 1 patient had and pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to or . One patient each was diagnosed with Alport syndrome due to and variants nephronophthisis due to variants, Fabry disease due to variants, and autosomal-dominant tubulointerstitial kidney disease due to variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with variant.

Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.

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