TY - JOUR
T1 - APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program
AU - the VA Million Veteran Program COVID-19 Science Initiative
AU - Hung, Adriana M.
AU - Shah, Shailja C.
AU - Bick, Alexander G.
AU - Yu, Zhihong
AU - Chen, Hua Chang
AU - Hunt, Christine M.
AU - Wendt, Frank
AU - Wilson, Otis
AU - Greevy, Robert A.
AU - Chung, Cecilia P.
AU - Suzuki, Ayako
AU - Ho, Yuk Lam
AU - Akwo, Elvis
AU - Polimanti, Renato
AU - Zhou, Jin
AU - Reaven, Peter
AU - Tsao, Philip S.
AU - Gaziano, J. Michael
AU - Huffman, Jennifer E.
AU - Joseph, Jacob
AU - Luoh, Shiuh Wen
AU - Iyengar, Sudha
AU - Chang, Kyong Mi
AU - Casas, Juan P.
AU - Matheny, Michael E.
AU - O'Donnell, Christopher J.
AU - Cho, Kelly
AU - Tao, Ran
AU - Susztak, Katalin
AU - Robinson-Cohen, Cassianne
AU - Tuteja, Sony
AU - Siew, Edward D.
AU - Muralidhar, Sumitra
AU - Beckham, Jean
AU - Pyarajan, Saiju
AU - Moser, Jennifer
AU - Thomann, Lauren
AU - Garcon, Helene
AU - Kosik, Nicole
AU - Liao, Katherine
AU - Damrauer, Scott
AU - Hauger, Richard
AU - Assimes, Themistocles
AU - Roussos, Panagiotis
AU - Striker, Robert
AU - Sun, Yan
AU - DuVall, Scott L.
AU - Lynch, Kristine E.
AU - Gatsby, Elise
AU - Song, Rebecca
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved
PY - 2022/4
Y1 - 2022/4
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85124144899&partnerID=8YFLogxK
U2 - 10.1001/jamainternmed.2021.8538
DO - 10.1001/jamainternmed.2021.8538
M3 - Article
C2 - 35089317
AN - SCOPUS:85124144899
SN - 2168-6106
VL - 182
SP - 386
EP - 395
JO - JAMA Internal Medicine
JF - JAMA Internal Medicine
IS - 4
ER -