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. 2022 Apr 1;182(4):386-395.
doi: 10.1001/jamainternmed.2021.8538.

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program

Adriana M Hung  1   2 , Shailja C Shah  3   4 , Alexander G Bick  5 , Zhihong Yu  6 , Hua-Chang Chen  6 , Christine M Hunt  7   8 , Frank Wendt  9   10 , Otis Wilson  11 , Robert A Greevy  6 , Cecilia P Chung  12 , Ayako Suzuki  7   8 , Yuk-Lam Ho  13 , Elvis Akwo  2 , Renato Polimanti  9   10 , Jin Zhou  14   15 , Peter Reaven  15   16 , Philip S Tsao  17   18 , J Michael Gaziano  13   19 , Jennifer E Huffman  20 , Jacob Joseph  21   22 , Shiuh-Wen Luoh  23   24 , Sudha Iyengar  25   26 , Kyong-Mi Chang  27 , Juan P Casas  13   28 , Michael E Matheny  29   30 , Christopher J O'Donnell  31   32   33 , Kelly Cho  13   28 , Ran Tao  6 , Katalin Susztak  34 , Cassianne Robinson-Cohen  11 , Sony Tuteja  27   35 , Edward D Siew  11   36 ; VA Million Veteran Program COVID-19 Science Initiative
Collaborators, Affiliations

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program

Adriana M Hung et al. JAMA Intern Med. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hung reports grants from Veterans Health CSR&D Merit Grant CX001897 and grants from Veterans Health MVP035 MVP COVID-19 Science Program during the conduct of the study; grants from Vertex Pharmaceutical outside the submitted work. Dr Bick reports personal fees from TenSixteen Bio outside the submitted work. Dr Hunt reports other from Akebia Therapeutics, Inc. Safety adjudication in COVID-19 clinical trial during the conduct of the study. Dr Wendt reports grants from NIMH outside the submitted work. Dr Akwo reports grants from American Heart Association Postdoc Award #20POST35210952/Akwo/2020 during the conduct of the study. Christopher J O'Donnell: Dr O'Donnell reports income from Novartis Institute for Biomedical Research as a salaried employee outside the submitted work. Dr Susztak reports grants from GSK, Regeneron, Bayer, BiPI, Novo Nordisk, Maze, Novartis, Gilead and other from AZ, Pfizer, Bayer, GSK Consulting outside the submitted work. Dr Siew reports grants from Veterans Health Services Research and Development Grant SDR 18-194 Million Veteran Program Gamma Program during the conduct of the study; personal fees from Akebia Therapeutics, Inc. Consultant on and personal fees from Da Vita, Inc. Honorarium for an invited educational talk on AKI epidemiology at the Da Vita Annual Physician Leadership Conference outside the submitted work; and Serves on the editorial board for the Clinical Journal of the American Society of Nephrology; and has received royalties as an author for UptoDate.

Figures

Figure 1.
Figure 1.. Flowchart for Patient Eligibility
Figure 2.
Figure 2.. Incidence of Acute Kidney Injury (AKI) and AKI Stages by APOL1 Risk Group
See this image and copyright information in PMC

References

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