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Introducing Genetic Tests With Uncertain Implications in Living Donor Kidney Transplantation: ApoL1 as a Case Study.
Progress in Transplantation 2016 September
Genetic mutations in apolipoprotein L1 (ApoL1) are associated with kidney disease. Apolipoprotein L1 mutations are common in African Americans (∼39% and 12% have 1 and 2 high-risk alleles, respectively). Carrying 2 ApoL1 risk alleles may explain much of the excess rate of kidney failure in African Americans compared to European Americans. Apolipoprotein L1 also has implications for kidney transplantation. Kidney grafts from deceased donors with 2 ApoL1 risk alleles have worse graft survival, but outcomes appear unaffected by recipient ApoL1 status. Unknown is whether donation increases the risk of kidney failure in living donors with 2 ApoL1 risk alleles and whether their donated kidneys have worse graft survival. There are 4 options to consider: (1) remain silent about ApoL1 risk alleles and renal failure and wait for more data; (2) counsel about race, ApoL1, and subsequent renal failure abstractly but remain agnostic about donor testing until more data are available; (3) provide counseling and encourage genotyping of prospective living donors of African ancestry as part of the living donor workup; or (4) mandate testing of all prospective living donors. We support option 3, and recommend, with donor permission, to discuss the results with potential recipients to promote informed decision-making. We also argue for a voluntary donor registry that collects long-term follow-up information. We provide ethical arguments to support these recommendations.
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