<i>APOL1</i> Variants, AKI, and Progression to Kidney Failure in People of African Ancestry Living with HIV.

Abstract

Acute kidney injury (AKI) is a common complication of HIV infection and associated with progression to kidney failure. We investigated associations between <i>Apolipoprotein L1</i> (<i>APOL1</i>) variants and AKI, and between AKI, <i>APOL1</i> variants and incident kidney failure, in people of African ancestry with HIV. We conducted a retrospective analysis of AKI (Kidney Disease: Improving Global Outcomes stages 2/3 and 3) in Genetic Markers of Kidney Disease Progression in People of African Ancestry with HIV (GEN-AFRICA) participants stratified by <i>APOL1</i> genotype (2 [G1G1, G1G2, G2G2], 1 [G1G0, G2G0] or 0 [G0G0] variants). Robust Poisson regression estimated AKI prevalence ratios (PR) within 3 months of cohort inception. Poisson regression with generalized estimating equations estimated AKI incidence rate ratios (IRR) during follow-up, adjusting for sex, age, time-updated cluster of differentiation 4 (CD4) count, HIV viral load, and kidney function. Cox proportional hazards models examined associations between AKI, <i>APOL1</i> variants, and incident kidney failure. Among 2701 participants (43% male; mean age 38.7 years; 12.7% with 2 APOL1 variants), 165 individuals experienced 183 AKI episodes. Participants with 2 APOL1 variants were more likely to experience AKI at cohort inception (adjusted PR 6.9, 95% CI: 3.5-13.8, <i>P</i> &lt; 0.001), had more severe AKI, and poorer recovery of kidney function post-AKI compared with those with 0 variants, but not during follow up. AKI was associated with incident kidney failure and this association varied by APOL1 status (<i>P</i> _interaction &lt; 0.001). Among people with HIV, 2 APOL1 variants were associated with increased risk of AKI, especially severe AKI at cohort inception, and poorer recovery of post-AKI. AKI identified individuals at increased risk of progression to kidney failure.