Aspirin use is associated with attenuated risk of severe acute kidney injury in septic patients: a dual-center retrospective analysis from MIMIC-IV and eICU cohorts

Sepsis is a systemic inflammatory response syndrome caused by infection, and sepsis-associated acute kidney injury (AKI) markedly increases mortality. Although aspirin's anti-inflammatory properties show therapeutic promise in sepsis, its specific renal protective effects in septic patients remain underexplored. This study investigated the association between aspirin exposure and severe acute kidney injury in septic patients using two databases: MIMIC-IV (73,181 ICU stays, 2008-2022), and eICU (200,859 ICU stays, 2014-2015). Among 45,562 septic patients, cohorts were stratified by aspirin exposure, and outcome variables were compared using multiple statistical adjustment methods including multivariable regression and propensity score analysis. The primary outcome was severe AKI incidence, with secondary outcomes including overall AKI, continuous renal replacement therapy (CRRT), and mortality. Our study suggests that aspirin exposure was associated with significantly lower severe AKI incidence in both databases (adjusted OR 0.35 in MIMIC-IV; 0.84 in eICU), representing risk reductions ranging from 16% to 65%. Secondary outcomes showed that aspirin exposure was associated with reduced kidney injury incidence, mortality rates and continuous renal replacement therapy requirements. These protective associations were consistent with sensitivity analyses and subgroup analyses. Furthermore, these protective effects were observed across different aspirin doses and formulations. However, aspirin may also increase the risk of thrombocytopenia and gastrointestinal bleeding. Our findings suggest that aspirin may be associated with reduced risk of sepsis-related kidney injury and mortality. Nevertheless, prospective randomized controlled trials are needed to confirm these associations, and individualized risk-benefit assessments remain essential before clinical application.