APOL1 Genotype and Patient Outcomes in US and South African Transplant Recipients With HIV who Received Kidneys From Donors With HIV

Background. Lower allograft survival has been demonstrated in kidney transplant recipients without HIV whose donors have 2 apolipoprotein L1 ( APOL1 ) renal risk variants (RRVs). The effects of APOL1 RRV on kidney transplant outcomes in people with HIV have not been fully assessed. Methods. Genomic DNA was analyzed for APOL1 RRV genotype using a probe-based assay in HIV-positive kidney transplant recipients (R + ) and their respective HIV-negative (D − ) or HIV-positive (D + ) kidney donors participating in HIV transplantation studies in South Africa (SA) and the United States (US). Allograft outcomes (time to first rejection, HIV-associated nephropathy, graft failure, or death) were compared by both donor and recipient RRV status. Results. Genomic DNA was available for 21 donors with HIV and 38 HIV D + /R + recipients in the SA cohort, and 57 donors (40 D + and 17 D − ) and 119 recipients (49 HIV D + /R + and 70 D − /R + ) in the US cohort. Recipient outcomes were not associated with recipient APOL1 genotype. However, recipients whose donor carried 1 versus 0 APOL1 RRV were significantly more likely to experience a negative composite outcome ( P < 0.02 for both cohorts independently), which led to an adjusted hazard ratio of a poor composite outcome of 2.9 (95% confidence interval, 1.1 to 7.4) and 10.1 (95% confidence interval, 2.4 to 42.7) in the SA and US cohorts, respectively. Conclusions. In two independent cohorts, the presence of 1 APOL1 RRV in a donor kidney led to significantly worse posttransplant outcomes. Further research into the interaction between the allograft environment and donor APOL1 genotype in people with HIV is required.