Journal Article

The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation

Bachmann, Nadine, Schüler, Markus, Grohmann, Maik, Schrezenmeier, Eva, Choi, Mira, Liefeldt, Lutz, Halleck, Fabian, Wagner, Timo, Weber, Ulrike, Budde, Klemens, Staeck, Oliver, Kremerskothen, Elisa, Bergmann, Carsten

2021

Overview

Chronic kidney disease (CKD) is a major health-care burden. Increasing evidence suggests that a considerable proportion of patients are affected by a monogenic kidney disorder. In this study, the kidney transplantation waiting list at the Charité was screened for patients with undetermined cause of CKD. By next-generation sequencing (NGS) we targeted all 600 genes described and associated with kidney disease or allied disorders. In total, 635 patients were investigated. Of these, 245 individuals had a known cause of CKD (38.5%) of which 119 had a proven genetic disease (e.g., ADPKD, Alport). The other 340 patients (53.5%) were classified as undetermined diagnosis, of whom 87 had kidney failure (KF) onset <40 years. To this latter group genetic testing was offered as well as to those patients (n = 29) with focal segmental glomerulosclerosis (FSGS) and all individuals (n = 21) suspicious for thrombotic microangiopathy (TMA) in kidney biopsy. We detected diagnostic variants in 26 of 126 patients (20.6%) of which 14 of 126 (11.1%) were pathogenic or likely pathogenic. In another 12 of 126 (9.5%) patients, variants of unknown significance (VUS) were detected. Our study demonstrates the diagnostic value of comprehensive genetic testing among patients with undetermined CKD.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: Adult / Biomedical and Life Sciences / Biomedicine / Genetic Testing / Glomerulosclerosis, Focal Segmental - epidemiology / Glomerulosclerosis, Focal Segmental - genetics / Human Genetics / Humans / Kidney / Kidney diseases / Kidney Transplantation / Kidney transplants / Laboratory Medicine / Polycystic Kidney, Autosomal Dominant / Renal Insufficiency, Chronic - diagnosis / Renal Insufficiency, Chronic - epidemiology / Renal Insufficiency, Chronic - genetics