APOL1genotype and patient outcomes in US and South African transplant recipients with HIV who received kidneys from donors with HIV

Importance

Lower kidney allograft survival has been demonstrated in kidney transplant recipients (KTR) without HIV whose donors have two apolipoprotein L1 (APOL1) renal risk variants (RRV). The effects ofAPOL1RRV on kidney transplant outcomes in people with HIV (PWH) have not been fully assessed.

Objective

To determine whetherAPOL1renal risk variants (G1/G2) in donors or recipients are associated with outcomes of kidney transplantation in people with HIV (PWH)?

Design

Comparative analysis of kidney allograft outcomes in two of the largest longitudinal clinical studies examining transplantation outcomes in PWH.

Setting and participants

Two cohorts of HIV-positive KTR (R+) and their respective HIV-negative (D-) or HIV-positive (D+) kidney donors from the South African (SA) HIV+ to HIV+ transplantation clinical study and the United States of America (US) HOPE in Action Kidney transplantation clinical trial. All patients with genomic DNA available forAPOL1genotyping were included.APOL1Genotype was determined using a probe-based assay.

Main outcomes measured

Time to first rejection, HIV-associated nephropathy, graft failure or death were compared by both donor and recipientAPOL1RRV 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 recipientAPOL1genotype. However, recipients whose donor carried one versus zeroAPOL1RRV 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% CI 1.1–7.4) and 10.1 (95% CI 2.4–42.7) in the SA and US cohorts, respectively.

Conclusions and relevance

In two independent studies, the presence of oneAPOL1RRV in a donor kidney led to significantly worse post-transplant outcomes while recipientAPOL1genotype was not associated with outcomes. Further research into the interaction between the allograft environment and donorAPOL1genotype in PWH is required.

KEY POINTS

Question

DoAPOL1renal risk variants (G1/G2) influence the outcomes of kidney transplantation in people with HIV (PWH)?

Findings

In two of the largest cohorts of PWH who are also kidney transplant recipients, the presence of even one donorAPOL1renal risk variant was associated with an adjusted hazard ratio of a poor composite outcome of 10.1 (95%CI=2.4-42.7) and 2.9 (95%CI=1.1-7.4) in the US and SA cohorts, respectively. RecipientAPOL1genotype was not associated with graft outcomes.

Meaning

This may have implications for allocation of allograft kidneys in PWH, as well as informing the need for therapies targetingAPOL1gene expression in kidney transplant recipients.