Association of Presepsis Statin Prescription With Kidney and Mortality Outcomes: Cause-Specific, Overlap-Weighted Analyses

초록

Rationale & Objective: Sepsis, complicated by kidney injury, poses a mortality risk in intensive care unit patients. Although statins are thought to offer protective effects against kidney injury through anti-inflammatory mechanisms, evidence remains inconclusive. This study aimed to evaluate whether statin prescription before sepsis onset affects the risks of kidney injury and mortality. Study Design: Retrospective cohort study. Setting & Participants: Adult intensive care unit patients who met Sepsis-3 criteria in Medical Information Mart for Intensive Care-IV. Exposure: Statin prescription within the 24 hours preceding sepsis onset. Outcomes: The primary outcome was the prespecified kidney outcome (need for kidney replacement therapy or a reduction in estimated glomerular filtration rate of ≥50%). Secondary outcomes were mortality without the kidney outcome (cause-specific) and overall mortality. Analytical Approach: We used overlap weighting to balance baseline characteristics. Cause-specific Cox models estimated associations for the kidney outcome and mortality without the kidney outcome; a weighted Cox model estimated associations for overall mortality. Results: The final cohort included 30,765 patients with sepsis, with 19.3% exposed to statins. Statin prescription was associated with a reduced risk of kidney outcome (HR, 0.83; 95% CI, 0.80-0.87), mortality without kidney outcome (HR, 0.56; 95% CI, 0.51-0.63), and overall mortality (HR, 0.78; 95% CI, 0.71-0.84). Subgroup analyses were broadly consistent across prespecified strata. For the kidney outcome, interaction testing suggested greater risk reduction among patients aged <65 years, those without chronic kidney disease, and those with hypertension. For death without prior kidney outcome and for overall mortality, protective associations were consistent across subgroups, with a larger effect among patients with prior myocardial infarction. Overall, statin prescription was consistently associated with lower risks of kidney outcome and mortality. Limitations: Single-database retrospective design and incomplete capture of sepsis severity measures. Conclusions: Presepsis statin prescription was associated with lower risks of kidney outcome and mortality, indicating potential clinical benefits in patients with sepsis. Plain-Language Summary: Sepsis is a severe infection that can threaten life and damage organs. Statins are medicines best known for lowering cholesterol, but they may also reduce inflammation and stabilize blood vessels. We studied adults in intensive care who met modern (Sepsis-3) criteria for sepsis and compared patients who were prescribed a statin within 24 hours before sepsis onset with those who were not. People who were taking statins before sepsis started had lower risks of kidney function decline and death. The association seemed stronger for survival than for kidney outcomes. These findings suggest that statins may offer clinical benefits for patients with sepsis and motivate future work to determine which statin types and doses are most helpful. © 2026 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

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