APOL1 Variants, AKI, and Progression to Kidney Failure in People of African Ancestry Living with HIV

Abstract

INTRODUCTION: Acute kidney injury (AKI) is a common complication of HIV infection and associated with progression to kidney failure. We investigated associations between Apolipoprotein L1 (APOL1) variants and AKI, and between AKI, APOL1 variants and incident kidney failure, in people of African ancestry with HIV. METHODS: 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 APOL1 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, APOL1 variants, and incident kidney failure. RESULTS: 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, P < 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 (P (interaction) < 0.001). CONCLUSION: 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.