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

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.

Retrospective cohort study.

Adult intensive care unit patients who met Sepsis-3 criteria in Medical Information Mart for Intensive Care-IV.

Statin prescription within the 24 hours preceding sepsis onset.

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.

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.

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.

Single-database retrospective design and incomplete capture of sepsis severity measures.

Presepsis statin prescription was associated with lower risks of kidney outcome and mortality, indicating potential clinical benefits in patients with sepsis.