Sequential genetic testing of living-related donors for inherited renal disease to promote informed choice and enhance safety of living donation

Transpl Int. 2021 Dec;34(12):2696-2705. doi: 10.1111/tri.14133. Epub 2021 Nov 3.

Abstract

Living kidney donors (LKDs) with a family history of renal disease are at risk of kidney disease as compared to LKDs without such history suggesting that some LKDs may be pre-symptomatic for monogenic kidney disease. LKDs with related transplant candidates whose kidney disease was considered genetic in origin were selected for genetic testing. In each case, the transplant candidate was first tested to verify the genetic diagnosis. A genetic diagnosis was confirmed in 12 of 24 transplant candidates (ADPKD-PKD1: 6, ALPORT-COL4A3: 2, ALPORT-COL4A5: 1: nephronophthisis-SDCCAG8: 1; CAKUT-HNF1B and ADTKD-MUC1: 1 each) and 2 had variants of unknown significance (VUS) in phenotype-relevant genes. Focused genetic testing was then done in 20 of 34 LKDs. 12 LKDs screened negative for the familial variant and were permitted to donate; seven screened positive and were counseled against donation. One, the heterozygous carrier of a recessive disorder was also cleared. Six of seven LKDs with a family history of ADPKD were under 30 years and in 5, by excluding ADPKD, allowed donation to safely proceed. The inclusion of genetic testing clarified the diagnosis in recipient candidates, improving safety or informed decision-making in LKDs.

Keywords: Alport nephropathy; chromosomal microarray; genetic testing; multiplex ligation-dependent probe amplification; next-generation sequencing; polycystic disease.

MeSH terms

  • Genetic Testing
  • Humans
  • Kidney Transplantation*
  • Living Donors
  • Phenotype
  • Polycystic Kidney, Autosomal Dominant* / diagnosis
  • Polycystic Kidney, Autosomal Dominant* / genetics