Shorter allograft survival is observed for kidneys transplanted from deceased African American donors relative to those from deceased European American donors. Recent retrospective reports have indicated that the presence of two apolipoprotein L1 gene (APOL1) renal-risk variants in the kidney donors significantly contributes to this disparity. APOL1 renal-risk variants are common in U.S. populations with African ancestry (primarily African Americans) and are strongly associated with end-stage renal disease for patients with non- diabetic kidney disease, yet these risk variants are rare in other ethnic groups. Before APOL1 genotypic data can be widely applied in the transplant community, however, a prospective multi-center study must be performed to evaluate outcomes of kidneys from donors with African ancestry. Critical clinical post-transplant information that was lacking in the prior retrospective studies needs to be collected, particularly kidney-biopsy data and key potential modifiers such as development of viral infections, donor-specific antibodies, and episodes of acute rejection. The NIH will fund a nationwide prospective study to assess the impact of APOL1 renal-risk variants on the outcomes of recipients of a kidney from a deceased or living donor with African ancestry and on the kidney health of living donors with African ancestry after nephrectomy. The study will consist of as many as 15 Clinical Centers and a central Scientific Data Research Center (SDRC). The Clinical Centers will collect one-time blood samples from each participant for APOL1 genotyping at the SDRC and will submit longitudinal clinical data for the recipients and living donors to the SDRC to assess the impact of APOL1 genotype on development of chronic kidney disease or end-stage renal disease. The results from this national study have the potential to transform organ allocation and informed consent processes in the transplantation of kidneys from donors with African ancestry, improve renal allograft survival, and provide a better understanding of the mechanisms whereby APOL1 renal-risk variants produce kidney disease.
Specific variants in the gene encoding apolipoprotein L1, which are generally restricted to persons with recent African ancestry, have been associated in retrospective analyses with increased risk of end-stage native- kidney disease and shorter survival of kidney transplants. The proposed prospective study will examine the impact of these variants on kidney-transplant recipients and donors, while taking into account various environmental or comorbid conditions that can cause kidney damage. The findings from this study have the potential to transform allocation of kidneys for transplantation, improve survival of transplanted kidneys, better inform potential kidney donors with recent African ancestry of the risks of donation, and provide a better understanding of the mechanisms whereby these genetic variants produce kidney disease.
| Freedman, Barry I; Julian, Bruce A (2018) Evaluation of Potential Living Kidney Donors in the APOL1 Era. J Am Soc Nephrol 29:1079-1081 |
