Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy

Abstract

Related living kidney donors (LKDs) are at higher risk of end‐stage renal disease (ESRD) compared with unrelated LKDs. A genetic panel was developed to screen 115 genes associated with renal diseases. We used this panel to screen six negative controls, four transplant candidates with presumed genetic renal disease and six related LKDs. After removing common variants, pathogenicity was predicted using six algorithms to score genetic variants based on conservation and function. All variants were evaluated in the context of patient phenotype and clinical data. We identified causal variants in three of the four transplant candidates. Two patients with a family history of autosomal dominant polycystic kidney disease segregated variants in PKD1. These findings excluded genetic risk in three of four relatives accepted as potential LKDs. A third patient with an atypical history for Alport syndrome had a splice site mutation in COL4A5. This pathogenic variant was excluded in a sibling accepted as an LKD. In another patient with a strong family history of ESRD, a negative genetic screen combined with negative comparative genomic hybridization in the recipient facilitated counseling of the related donor. This genetic renal disease panel will allow rapid, efficient and cost‐effective evaluation of related LKDs.

Initial experience from a renal genetics clinic demonstrates a distinct role in patient management

“…With KidneySeq™, targeted capture of coding exons and splice sites of renal disease genes are performed with RNA baits and then subjected to massively parallel sequencing and bioinformatic processing as previously described. 3,7 For one patient, testing for Fabry disease (OMIM 301500) was performed at Mount Sinai, New York, and for another patient, testing was limited to APOL1 risk alleles, G1 and G2 (IIHG). Outcomes of patients who underwent genetic testing with positive results are shown in Table 1.…”

“…Additionally, in the field of living related renal transplantation identifying the genetic basis of kidney disease in the patient with end-stage renal disease (ESRD) can assist in the screening of the related living donor. 3 Testing living donors of recent African ancestry for the APOL1 risk alleles G1 and G2 is also a consideration, given the emerging data on the risk of kidney disease. 4,5 To help with a perceived need within our own practice, we established a Renal Genetics Clinic (RGC) with physicians who had a strong interest and clinical expertise in a broad range of renal genetic disorders and a CGC whose practice was limited to nephrology and cardiology.…”

Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage

“…7 • Develop better strategies and tools to screen donor candidates for genetic kidney diseases that consider the accuracy, efficiency and costs of testing, including assessment of targeted gene panels for known mutations implicated in kidney diseases. 392 • Develop reliable imaging criteria to exclude ADPKD in donor candidates based on the results of the CT angiogram, which is frequently used to assess the renal vasculature as a routine part of the donor evaluation. • Define the role APOL1 genotyping in the evaluation of donor candidates of sub-Saharan African ancestry.…”

Tissue donation and transplantation program in Sri Lanka : a medico-legal point of view

“…8 In cases where living organ donors are genetically related to the recipient there is a considerable risk of the recipient acquiring genetically related disorders later in life due to shared inheritance of genetic variants or common environmental exposure that increases susceptibility to organ failure. 9 Related living kidney donors are at higher risk of end-stage renal disease compared with unrelated living kidney donors. 9 Living organ donations have several ethical considerations.…”

“…9 Related living kidney donors are at higher risk of end-stage renal disease compared with unrelated living kidney donors. 9 Living organ donations have several ethical considerations. During transplantation, the transplantation surgeon may endanger the life of a healthy individual to save the life of the patient.…”