Session Time: 3:15pm-4:45pm
Presentation Time: 3:27pm-3:39pm
*Purpose: Living kidney donors (LKDs) with a family history of kidney disease are at higher risk of end-stage renal disease (ESRD) compared to LKDs without a positive family history, likely reflecting the inheritance of shared disease alleles. The objective of this study was to determine if screening LKDs for genetic disease would improve donor evaluation and promote informed choice and donor safety.
*Methods: Living donors with related recipient candidates whose cause of ESRD was probably or likely genetic in origin were selected for genetic counseling and screening as part of their donor evaluation. In each case the recipient candidate was first tested with a targeted or a comprehensive screening strategy to verify the genetic diagnosis. If a genetic diagnosis was confirmed, then focused or cascade screening was done for the related LKD.
*Results: A total of 16 recipient candidates with 20 related living donors were selected for screening. A genetic diagnosis was confirmed in 8 patients (ADPKD-PKD1: 4, ALPORT-COL4A3: 2, ALPORT-COL4A5: 1 and ADTKD-MUC1: 1) and 2 candidates had variants of unknown significance (VUS) in phenotype relevant genes. Of 20 related living donor candidates, cascade screening was done for 16 whose related recipient had a confirmed genetic diagnosis. Of these, 10 LKDs screened negative for the familial variant and were permitted to donate, 6 screened positive and were counseled against donation. All 6 LKDs with a family history of ADPKD were asymptomatic and between 20 and 30 yr. old. In 5 of them, ADPKD was excluded by negative genetic screening, a situation where a normal renal ultrasound has a negative predictive value of only ~ 90%. 3 of 3 recipients with confirmed COL4 nephropathy had no syndromic features to suggest Alport syndrome and all 3 of their LKDs with microscopic hematuria and a normal eGFR tested positive by genetic screening. In 4 other LKDs, genetic screening could not be done as a diagnosis was not established in their related recipients and these LKDs were permitted to donate after counseling.
*Conclusions: The inclusion of genetic testing in recipient candidates clarified their diagnosis, permitted screening and exclusion of disease in LKDs, facilitated genetic counseling and helped LKDs make informed decisions.
To cite this abstract in AMA style:Thomas CP, Freese ME, Katz DA. Genetic Testing of Living Related Donors for Inherited Renal Disease Improves Evaluation and Promotes Informed Choice of At-Risk Living Donors [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/genetic-testing-of-living-related-donors-for-inherited-renal-disease-improves-evaluation-and-promotes-informed-choice-of-at-risk-living-donors/. Accessed March 6, 2021.
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