*Purpose: Genetic testing is an emerging tool for ‌the evaluation of patients with end-stage renal disease (ESRD). In kidney transplantation (KT), testing can identify disease characteristics of recipients and in genetic risk stratification as a part of living donor selection. Here we demonstrate the utility of broad-panel genetic testing in both pre and post-KT individuals at an academic transplant center.

*Methods: Samples were collected from patients either waitlisted for KT (pre-KT) or KT recipients (post-KT). Criteria for testing pre-KT patients included ESRD with either early onset, an unclear etiology, or those with a positive family history. Genetic testing was performed on post-KT patients with suspected recurrent disease or poor graft function.

Samples were tested via a commercially available Next-Generation Sequencing (NGS) panel of >380 genes associated with isolated or syndromic Chronic Kidney Disease (CKD). Positive results included at least one pathogenic (P) or likely pathogenic (LP) variant in an autosomal dominant or X-linked gene, two P/LP variants in an autosomal recessive gene, or the presence of two APOL1 risk alleles.

*Results: This study included 89 tested patients (pre-KT=83, post-KT=6) who ranged in age from 20 to 77 years (median: 41 years), and were predominantly African American (62/89). A total of 41 positive findings were identified in 37 patients, including 50% (3/6) of post-KT and 41% (34/83) of pre-KT patients. Positive findings spanned 11 genes. Three genes (APOL1, COL4A5, NPHP1) were positive in >1 patient, while eight genes were represented by a single positive. The majority of positive findings occurred in APOL1 (29/41). Among those positive for APOL1, 4 patients had a co-occurring positive in a second gene (COL4A5, FGFR1, PKD1, SLC5A2).

Findings resulted in reclassification or confirmation of the cause of ESRD in 37% (31/83) of pre-KT patients. Genetic testing significantly altered management and possibly prevented graft damage in at least one post-KT patient through the identification of a previously undiagnosed case of Adenine Phosphoribosyltransferase Deficiency.

*Conclusions: Use of a‌ ‌broad‌ genetic testing panel‌ i‌n‌ a largely ‌African‌ ‌American‌ cohort‌ ‌of‌ ‌pre- and post-KT patients‌ identified‌ ‌P/LP variants in‌‌ a variety of genes associated with common‌ and ‌rare‌ heritable ‌kidney‌ ‌diseases. Identification of ESRD cause in pre-KT patients allows for informed prognostication and identification and testing of at-risk family members, including potential living-related donors. Post-KT testing can have implications for disease recurrence and overall graft health. Expanding our understanding of monogenic contributors to ESRD, through integration of renal genetic testing in the KT setting, will continue to enhance pre- and post-KT management.

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