Abstract: SA-PO533
Clinical Utility of Genetic Testing in Kidney Transplant Evaluation
Session Information
- Genetic Diseases: Diagnosis
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Bhalla, Anshul, James D. Eason Transplant Institute, Memphis, Tennessee, United States
- Raible, Darbey, Natera, Inc., Austin, Texas, United States
- Balaraman, Vasanthi, James D. Eason Transplant Institute, Memphis, Tennessee, United States
- Talwar, Manish, James D. Eason Transplant Institute, Memphis, Tennessee, United States
Background
Genetic testing is an emerging tool in kidney transplant (KT) evaluation. We present examples of diagnostic and clinical utility resulting from broad-panel genetic testing in pre- and post-KT settings at an academic transplant center.
Methods
Selection criteria for genetic testing included: pre-KT patients with early-onset end stage kidney disease (ESKD), ESKD of unclear etiology or positive family history of ESKD, and post-KT patients with suspected recurrent disease or poor graft function. Patients were tested using a Next-Generation Sequencing (NGS) panel of 385 genes (the RenasightTM Test) 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 132 patients (pre-KT=98, post-KT=34). The median age was 42 years (range: 21-77) and most (78%) were African American. Overall, 62 patients (47%) received a positive result in at least one panel gene.
Hypertensive nephrosclerosis was the most common diagnosis (68%, n=90) at the time of referral for KT evaluation. Genetic findings established a new diagnosis in 57% (n=51/90) of these patients. Genetic testing confirmed the diagnosis for 2 of 36 patients with an established a priori clinical diagnosis other than hypertensive nephrosclerosis and led to further delineation of disease origin in 6 (17%) of these patients.
Surveillance changes were indicated for 27% of patients, based on risk for recurrence post-KT (n=11) and/or extrarenal features (n=6) delineated via genetic testing. Significant alterations to treatment were indicated for 2 (unrelated) patients with previously undiagnosed Adenine Phosphoribosyltransferase (APRT) Deficiency, for whom treatment with xanthine oxidase inhibitor was initiated to reduce risk of graft damage and loss.
Conclusion
In KT, genetic diagnosis can facilitate personalized prognostication of disease recurrence and changes in management to optimize graft survival. Demonstration of real-world clinical benefits is important for establishing evidence-based guidelines and best practices for integration of genetic testing into KT evaluation.