The Diagnostic Yield of Genomic Sequencing-Based Genetic Kidney Disease Testing in Kidney Transplant Candidates: Experience at an Urban US Transplant Center.

Abstract

Background: Recent studies suggest that approximately 10% of patients with chronic kidney disease (CKD) have disease-causing genetic variants, an observation relevant to evaluation of kidney transplant candidates.

Methods: We retrospectively investigated the diagnostic yield of genetic testing in kidney transplant candidates evaluated at our program (January 1, 2021-December 8, 2022). Inclusion criteria were as follows: first-degree relative(s) with CKD/end-stage kidney disease (ESKD), early-onset CKD, focal segmental glomerulosclerosis, cystic kidney disease, alternative complement pathway-associated diseases, or ESKD of unknown cause.

Results: One hundred eleven patients underwent genetic kidney disease testing. The most common indication for testing was early-onset CKD (34.2%), followed by a family history of CKD (23.4%), focal segmental glomerulosclerosis (18.0%), cystic kidney disease (9.0%), alternative complement pathway diseases (3.6%), and ESKD of unknown cause (11.7%). Overall diagnostic yield was 46.9% (52/111), and yield was highest among candidates with a family history of CKD (61.5%; 16/26). Among cases with positive testing, the most common diagnostic variant was APOL1, with 2 renal risk variants identified in 57.7% (30/52), while monogenic causes of CKD were identified in 42.3% (22/52). Genetic testing led to further evaluation or to a different diagnosis than the initial clinical diagnosis in 8.1% (9/111) of the cohort. For 24 transplant candidates, their identified diagnostic variants indicated the need for genetic testing of related living donor candidates; of these, 6 living donor candidates were evaluated and underwent testing, of whom donation was excluded in 1 candidate.

Conclusions: Pretransplant genetic testing increases understanding of CKD cause, and provides information for living donor evaluation and risk assessment of posttransplant disease recurrence.