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

CME Credits: 1.00

Released: 2022-01-28

Key Points

Question Are APOL1 high-risk genotypes observed in individuals with African ancestry associated with acute kidney injury (AKI) and death following hospitalization for COVID-19?
Findings In this cohort of 990 veterans with African ancestry hospitalized with COVID-19, 1 in 8 had APOL1 high-risk genotypes. Of those with high-risk genotypes, 51.2% had AKI, and 19.2% died, suggesting that high-risk genotype may be associated with a 2-fold increase in the odds of severe AKI and death; this increased risk was observed even in patients with normal kidney function prior to COVID-19.
Meaning APOL1 high-risk genotypes were associated with increased odds of AKI, AKI severity, and death in individuals with African ancestry hospitalized with COVID-19.

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.


Educational Objective
To identify the key insights or developments described in this article


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