APOL1 risk variants, AKI, and death in black veterans with COVID-19

Background: Health disparities exist in rates of acute kidney injury (AKI) and death related to COVID-19. Black patients with two copies of apolipoprotein L1 (APOL1) variants G1 or G2 have significantly increased rates of renal disease. It is unknown whether APOL1 is associated with an increased risk for AKI in COVID-19 infection. Methods: We performed a retrospective study of 990 Black patients in the VA Million Veteran Program hospitalized with COVID-19 between March 2020 and January 2021. The primary exposure was having 2 APOL1 risk variants (APOL1 high-risk group), compared to having 1 or 0 risk variants (APOL1 low-risk group). The primary outcome was AKI. The secondary outcomes were AKI severity stages and death. We performed a subgroup analysis in individuals with eGFR> 60 ml/min/1.73m2. Results: 392 (39.6%) patients developed AKI, 28 (7%) required dialysis and 122 (12.3%) died. Patients categorized as APOL1 high-risk group had a significantly higher risk of AKI (adjusted odds ratio [OR] 1.98;95% confidence interval [CI]: 1.29-3.05;p=0.002), higher AKI severity stages (OR 2.06;95% CI: 1.39-3.04;p<0.001) and death (OR 2.15;95% CI: 1.23-3.67;p=0.006). The association with AKI persisted in the subgroup with normal kidney function (OR 1.92;95% CI: 1.15-3.22;p=0.01). Figure 1. shows the proportion of patients by AKI stages according to APOL1 risk group. Conclusions: APOL1 renal risk variants were associated with higher risk of AKI, AKI severity, and death in Black Veterans hospitalized with COVID-19, even amongst individuals with prior normal kidney function. We identify a specific genetic contribution to COVID-19 health disparities.