Adriana M Hung1,2, Shailja C Shah3,4, Alexander G Bick5, Zhihong Yu6, Hua-Chang Chen6, Christine M Hunt7,8, Frank Wendt9,10, Otis Wilson11, Robert A Greevy6, Cecilia P Chung12, Ayako Suzuki7,8, Yuk-Lam Ho13, Elvis Akwo2, Renato Polimanti9,10, Jin Zhou14,15, Peter Reaven15,16, Philip S Tsao17,18, J Michael Gaziano13,19, Jennifer E Huffman20, Jacob Joseph21,22, Shiuh-Wen Luoh23,24, Sudha Iyengar25,26, Kyong-Mi Chang27, Juan P Casas13,28, Michael E Matheny29,30, Christopher J O'Donnell31,32,33, Kelly Cho13,28, Ran Tao6, Katalin Susztak34, Cassianne Robinson-Cohen11, Sony Tuteja27,35, Edward D Siew11,36. 1. Tennessee Valley Healthcare System, Nashville Campus, Nashville. 2. Division of Nephrology & Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee. 3. GI Section, VA San Diego Healthcare System, San Diego, California. 4. Division of Gastroenterology, University of California, San Diego, San Diego. 5. Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 6. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. 7. Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina. 8. VA Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina. 9. Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut. 10. VA CT Healthcare Center, West Haven, Connecticut. 11. Division of Nephrology & Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 12. Division of Rheumatology and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Rheumatology Section, Veterans Affairs, Nashville, Tennessee. 13. Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston. 14. Department of Epidemiology and Biostatistics, University of Arizona, Phoenix. 15. Phoenix VA Health Care System, Phoenix, Arizona. 16. Division of Endocrinology, Department of Medicine, University of Arizona, Phoenix. 17. Epidemiology Research and Information Center (ERIC), VA Palo Alto Health Care System, Palo Alto, California. 18. Department of Medicine, Stanford University School of Medicine, Palo Alto, California. 19. Division of Aging, Brigham & Women's Hospital, Boston, Massachusetts. 20. Center for Population Genomics, Massachusetts Veterans Epidemiology Research & Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts. 21. Cardiology Section, Veterans Affairs Boston, Boston, Massachusetts. 22. Division of Cardiovascular Medicine, Brigham & Women's Hospital, Boston, Massachusetts. 23. VA Portland Health Care System, Portland, Oregon. 24. Knight Cancer Institute, Oregon Health & Science University, Portland. 25. Department of Population and Quantitative Health Sciences, Case Western Reserve University and Louis Stoke, Cleveland VA, Cleveland, Ohio. 26. Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio. 27. The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. 28. Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts. 29. Departments of Biomedical Informatics, Biostatistics, and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 30. GREEC, TVHS VA, Nashville, Tennessee. 31. Cardiology, VA Boston Healthcare System, Boston, Massachusetts. 32. Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 33. Novartis. 34. Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. 35. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 36. Tennessee Valley Healthcare System, Nashville VA Medical Center, Nashville, Tennessee.
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.
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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