<i>APOL1</i> Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program
Authors: Adriana M. Hung, Shailja C. Shah, Alexander G. Bick, Zhihong Yu, Hua-Chang Chen, Christine M. Hunt, Frank Wendt, Otis Wilson, Robert A. Greevy, Cecilia P. Chung, Ayako Suzuki, Yuk-Lam Ho, Elvis Akwo, Renato Polimanti, Jin Zhou, Peter Reaven, Philip S. Tsao, J. Michael Gaziano, Jennifer E. Huffman, Jacob Joseph, Shiuh-Wen Luoh, Sudha Iyengar, Kyong-Mi Chang, Juan P. Casas, Michael E. Matheny, Christopher J. O’Donnell, Kelly Cho, Ran Tao, Katalin Susztak, Cassianne Robinson-Cohen, Sony Tuteja, Edward D. Siew, Adriana Hung, Agnes Wallbom, Ana Palacio, Brooks Robey, Darshana Jhala, Daryl Fujii, David Cohen, Edward Boyko, Frank Jacono, Gerardo Villareal, Helene Garcon, J. Michael Gaziano, Jack Lichy, James Norton, Jean Beckham, Jeffrey Whittle, Jennifer Huffman, Jennifer Moser, Jennifer Greco, Jessica Walsh, John Harley, John Wells, Jon Klein, Jonathan Moorman, Joseph Constans, Joseph Fayad, Juan P. Casas, Junzhe Xu, Katherine Liao, Kathrina Alexander, Kelly Cho, Kimberly Hammer, Kris Oursler, Kristin Mattocks, Kyong-Mi Chang, Louis Dellitalia, Mark Hamner, Mary Whooley, Maureen Murdoch, Melinda Gaddy, Michael Godschalk, Michael Rauchman, Mostaqul Huq, Neeraj Tandon, Nicole Kosik, Nora Ratcliffe, Olaoluwa Okusaga, Panagiotis Roussos, Patrick Strollo, Paul Meyer, Peruvemba Sriram, Peter Wilson, Peter Liang, Philip S. Tsao, Prakash Balasubramanian, Rachel Ramoni, Rachel McArdle, Richard Hauger, Richard Servatius, River Smith, Robert Striker, Roy Mathew, Saib Gappy, Saiju Pyarajan, Salvador Gutierrez, Samir Gupta, Samuel Aguayo, Satish Sharma, Scott Damrauer, Scott Kinlay, Shing Yeh, Shiuh-Wen Luoh, Sony Tuteja, Stephen Mastorides, Sudha Iyengar, Sujata Bhushan, Sumitra Muralidhar, Sunil Ahuja, Suthat Liangpunsakul, Themistocles Assimes, Timothy Morgan, Todd Stapley, Yan Sun, Zuhair Ballas
Journal: JAMA Internal Medicine (2022)

Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates.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.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.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).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).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.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.