tetano
Editor, Senior Moderator
JAMA Intern Med
. 2022 Jan 28.
doi: 10.1001/jamainternmed.2021.8538. Online ahead of print.
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[SUP] 1 2 [/SUP], Shailja C Shah[SUP] 3 4 [/SUP], Alexander G Bick[SUP] 5 [/SUP], Zhihong Yu[SUP] 6 [/SUP], Hua-Chang Chen[SUP] 6 [/SUP], Christine M Hunt[SUP] 7 8 [/SUP], Frank Wendt[SUP] 9 10 [/SUP], Otis Wilson[SUP] 11 [/SUP], Robert A Greevy[SUP] 6 [/SUP], Cecilia P Chung[SUP] 12 [/SUP], Ayako Suzuki[SUP] 7 8 [/SUP], Yuk-Lam Ho[SUP] 13 [/SUP], Elvis Akwo[SUP] 2 [/SUP], Renato Polimanti[SUP] 9 10 [/SUP], Jin Zhou[SUP] 14 15 [/SUP], Peter Reaven[SUP] 15 16 [/SUP], Philip S Tsao[SUP] 17 18 [/SUP], J Michael Gaziano[SUP] 13 19 [/SUP], Jennifer E Huffman[SUP] 20 [/SUP], Jacob Joseph[SUP] 21 22 [/SUP], Shiuh-Wen Luoh[SUP] 23 24 [/SUP], Sudha Iyengar[SUP] 25 26 [/SUP], Kyong-Mi Chang[SUP] 27 [/SUP], Juan P Casas[SUP] 13 28 [/SUP], Michael E Matheny[SUP] 29 30 [/SUP], Christopher J O'Donnell[SUP] 31 32 33 [/SUP], Kelly Cho[SUP] 13 28 [/SUP], Ran Tao[SUP] 6 [/SUP], Katalin Susztak[SUP] 34 [/SUP], Cassianne Robinson-Cohen[SUP] 11 [/SUP], Sony Tuteja[SUP] 27 35 [/SUP], Edward D Siew[SUP] 11 36 [/SUP], VA Million Veteran Program COVID-19 Science Initiative
Collaborators, Affiliations
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.
. 2022 Jan 28.
doi: 10.1001/jamainternmed.2021.8538. Online ahead of print.
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[SUP] 1 2 [/SUP], Shailja C Shah[SUP] 3 4 [/SUP], Alexander G Bick[SUP] 5 [/SUP], Zhihong Yu[SUP] 6 [/SUP], Hua-Chang Chen[SUP] 6 [/SUP], Christine M Hunt[SUP] 7 8 [/SUP], Frank Wendt[SUP] 9 10 [/SUP], Otis Wilson[SUP] 11 [/SUP], Robert A Greevy[SUP] 6 [/SUP], Cecilia P Chung[SUP] 12 [/SUP], Ayako Suzuki[SUP] 7 8 [/SUP], Yuk-Lam Ho[SUP] 13 [/SUP], Elvis Akwo[SUP] 2 [/SUP], Renato Polimanti[SUP] 9 10 [/SUP], Jin Zhou[SUP] 14 15 [/SUP], Peter Reaven[SUP] 15 16 [/SUP], Philip S Tsao[SUP] 17 18 [/SUP], J Michael Gaziano[SUP] 13 19 [/SUP], Jennifer E Huffman[SUP] 20 [/SUP], Jacob Joseph[SUP] 21 22 [/SUP], Shiuh-Wen Luoh[SUP] 23 24 [/SUP], Sudha Iyengar[SUP] 25 26 [/SUP], Kyong-Mi Chang[SUP] 27 [/SUP], Juan P Casas[SUP] 13 28 [/SUP], Michael E Matheny[SUP] 29 30 [/SUP], Christopher J O'Donnell[SUP] 31 32 33 [/SUP], Kelly Cho[SUP] 13 28 [/SUP], Ran Tao[SUP] 6 [/SUP], Katalin Susztak[SUP] 34 [/SUP], Cassianne Robinson-Cohen[SUP] 11 [/SUP], Sony Tuteja[SUP] 27 35 [/SUP], Edward D Siew[SUP] 11 36 [/SUP], VA Million Veteran Program COVID-19 Science Initiative
Collaborators, Affiliations
- PMID: 35089317
- DOI: 10.1001/jamainternmed.2021.8538
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.