Abstract
Importance
Two risk variants in the apolipoprotein L1 gene ( APOL1 ) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease.
Objective
To examine the association between APOL1 high-risk genotypes and the risk of sepsis and sepsis-related phenotypes in patients hospitalized with infections.
Design, setting, and participants
A retrospective cohort study of 2,242 Black patients hospitalized with infections.
Exposures
Carriage of APOL1 high-risk genotypes.
Main outcomes and measures
The primary outcome was sepsis; secondary outcomes were short-term mortality and organ failure related to sepsis.
Results
Of 2,242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00–1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR=1.14 [95% CI, 0.88-1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR=0.99 [95% CI, 0.70-1.39; p=0.95]. APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR=1.64 [95% CI, 1.21–2.22; p=0.001], but not with other sepsis-related organ dysfunction or short-term mortality. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR=1.36 [95% CI, 1.00–1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR=1.16 [95% CI, 0.74–1.81; p=0.52]).
Conclusion and relevance
APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing severe renal disease.
Full Text Availability
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