Clinical Utility of Standardized Genetic Testing in Kidney Transplant Candidate Evaluation

Genetic testing is increasingly used in the evaluation of kidney transplant (KT) candidates, yet its direct association with transplant-related outcomes remains unclear. This study assessed whether genetic test results are associated with key steps in the KT process.

In this observational cohort study, 270 KT candidates underwent standardized genetic testing between January 2021 and November 2024. The outcomes, including waitlisting and transplantation, were compared between candidates with and without positive results. Primary outcomes assessed clinical utility during transplant evaluation, including diagnostic reclassification of end-stage kidney disease (ESKD), effects on living donor evaluation, and genetic counseling. Secondary outcomes included waitlisting, transplantation, and post-transplant allograft function (estimated glomerular filtration rate).

Among 270 KT candidates, indications for testing included family history (45.9%), hypertension-attributed ESKD without biopsy (30%), and ESKD of unknown etiology (24.4%). Positive genetic results were identified in 104 candidates (38.5%), who were younger and more frequently Black. Family history independently predicted a positive result (adjusted odds ratio = 1.91 and 95% confidence interval, 1.13-3.27; P = 0.02). Genetic kidney disease was identified in 36.4% of candidates with ESKD of unknown etiology and 43.2% of those with hypertension-attributed ESKD, most commonly APOL1-mediated disease. APOL1 high-risk genotypes were present in 50% of focal segmental glomerulosclerosis cases. Overall, 75.9% received pretest counseling and positive results (n = 104) prompted post-test counseling (n = 85) and guided living donor risk assessment and evaluation for extrarenal manifestations. During follow-up, waitlisting, transplantation rates, and post-transplant estimated glomerular filtration rate did not differ between candidates with and without positive results (P = 0.72, P = 0.35, and P = 0.06, respectively).

Genetic testing demonstrated a high diagnostic rate among KT candidates, particularly in identifying APOL1-associated risk. Testing clarified disease etiology, informed recipient and family counseling, and supported safe living donor selection without affecting waitlisting. Integrating genetic testing into transplant evaluation may enhance precision medicine and transplant care.