Association between APOL1 risk variants and progression from infection to sepsis

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 either progression from infection to sepsis or sepsis-related phenotypes, independent of their association with severe renal disease. Objective To examine the association between APOL1 high-risk genotypes and the risk of progression from infection to sepsis and sepsis-related phenotypes. Design, setting, and participants A retrospective cohort study of 2,242 Black patients hospitalized with an infection. Exposures Carriage of APOL1 high-risk genotypes. Main outcomes and measures The primary outcome was sepsis; secondary outcomes were death 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 death. 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 renal disease.