Hung, Adriana M., Shah, Shailja C., Bick, Alexander G., Yu, Zhihong, Chen, Hua-Chang, Hunt, Christine M., Wendt, Frank, Wilson, Otis, Greevy, Robert A., Chung, Cecilia P., Suzuki, Ayako, Ho, Yuk-Lam, Akwo, Elvis, Polimanti, Renato, Zhou, Jin, Reaven, Peter, Tsao, Philip S., Gaziano, J. Michael, Huffman, Jennifer E., Joseph, Jacob, Luoh, Shiuh-Wen, Iyengar, Sudha, Chang, Kyong-Mi, Casas, Juan P., Matheny, Michael E., O’Donnell, Christopher J., Cho, Kelly, Tao, Ran, Susztak, Katalin, Robinson-Cohen, Cassianne, Tuteja, Sony, and Siew, Edward D.
IMPORTANCE: 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 m(2)). 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