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Master of Public Health

Association between risk variants and progression from infection to sepsis

AUTHORS

Jiang L , Liu G , Oeser A , Ihegword A , Dickson AL , Daniel LL , Hung AM , Cox NJ , Chung CP , Wei WQ , Stein CM , Feng Q , . medRxiv : the preprint server for health sciences. 2023 1 28; ().

ABSTRACT

IMPORTANCE: Two risk variants in the apolipoprotein L1 gene ( ) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether 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 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 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 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]. 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 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: high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing renal disease.

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