Hung, Adriana M.Shah, Shailja C.Bick, Alexander G.Yu, ZhihongChen, Hua-ChangHunt, Christine M.Wendt, FrankWilson, OtisGreevy, Robert A.Chung, Cecilia P.Suzuki, AyakoHo, Yuk-LamAkwo, ElvisPolimanti, RenatoZhou, JinReaven, PeterTsao, Philip S.Gaziano, J. MichaelHuffman, Jennifer E.Joseph, JacobLuoh, Shiuh-WenIyengar, SudhaChang, Kyong-MiCasas, Juan P.Matheny, Michael E.O'Donnell, Christopher J.Cho, KellyTao, RanSusztak, KatalinRobinson-Cohen, CassianneTuteja, SonySiew, Edward D.VA Million Veteran Program COVID-19 Science Initiative2024-11-262024-11-262022Hung AM, Shah SC, Bick AG, et al. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program. JAMA Intern Med. 2022;182(4):386-395. doi:10.1001/jamainternmed.2021.8538https://hdl.handle.net/1805/44722Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease. We tested the hypothesis that the APOL1 high-risk group is associated with a higher-risk of COVID-19-associated AKI and death. Design, setting, and participants: This retrospective cohort study included 990 participants with African ancestry enrolled in the Million Veteran Program who were hospitalized with COVID-19 between March 2020 and January 2021 with available genetic information. Exposures: The primary exposure was having 2 APOL1 risk variants (RV) (APOL1 high-risk group), compared with having 1 or 0 risk variants (APOL1 low-risk group). Main outcomes and measures: The primary outcome was AKI. The secondary outcomes were stages of AKI severity and death. Multivariable logistic regression analyses adjusted for preexisting comorbidities, medications, and inpatient AKI risk factors; 10 principal components of ancestry were performed to study these associations. We performed a subgroup analysis in individuals with normal kidney function prior to hospitalization (estimated glomerular filtration rate ≥60 mL/min/1.73 m2). Results: Of the 990 participants with African ancestry, 905 (91.4%) were male with a median (IQR) age of 68 (60-73) years. Overall, 392 (39.6%) patients developed AKI, 141 (14%) developed stages 2 or 3 AKI, 28 (3%) required dialysis, and 122 (12.3%) died. One hundred twenty-five (12.6%) of the participants were in the APOL1 high-risk group. Patients categorized as APOL1 high-risk group had significantly higher odds of AKI (adjusted odds ratio [OR], 1.95; 95% CI, 1.27-3.02; P = .002), higher AKI severity stages (OR, 2.03; 95% CI, 1.37-2.99; P < .001), and death (OR, 2.15; 95% CI, 1.22-3.72; P = .007). The association with AKI persisted in the subgroup with normal kidney function (OR, 1.93; 95% CI, 1.15-3.26; P = .01). Data analysis was conducted between February 2021 and April 2021. Conclusions and relevance: In this cohort study of veterans with African ancestry hospitalized with COVID-19 infection, APOL1 kidney risk variants were associated with higher odds of AKI, AKI severity, and death, even among individuals with prior normal kidney function.en-USPublisher PolicyAcute kidney injuryCOVID-19HospitalizationRisk factorsVeteransArticle