Endothelial Activation and Stress Index Elevation Associated with Adverse Prognosis in Sepsis-associated acute kidney injury Patients: Validation Based on Two Critical Care Cohorts

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prevalent complication in critical care settings with high mortality. Early identification of high-risk patients is crucial. The Endothelial Activation Stress Index (EASIX) has been studied in other conditions but not in SA-AKI. This study evaluates EASIX's association with short-term mortality in SA-AKI patients. Methods: In this retrospective cohort study, data from 12,267 SA-AKI patients in MIMIC-IV were analyzed. EASIX was categorized using curve fitting and inflection point analysis. Propensity score matching (PSM), overlap weighting (OW), pair algorithm (PA), and inverse probability of treatment weight (IPTW) ensured data balance. Cox models, Kaplan-Meier analysis, subgroup analyses, ROC Curves and E-value assessments were used to examine the relationship between EASIX and outcomes. Furthermore, we validated these findings using the eICU database. Results: A non-linear association between EASIX and 28-day mortality was found, with an inflection point at 10.83. PSM balanced covariates. Kaplan-Meier analysis showed significantly lower survival in the high EASIX group (P < 0.001 pre-PSM, P = 0.002 post-PSM). Post-PSM, the high EASIX group had higher 28-day mortality (42.9% vs. 32.9%), in-hospital mortality (40.5% vs. 30.8%), and ICU mortality (29.6% vs. 20.4%; all P < 0.001). Multivariable regression and weighting methods (IPTW, PA, OW) confirmed the increased mortality risk. Subgroup and E-value analyses further validated these findings. ROC analysis yielded an AUC for 28-day mortality, outperforming SOFA and other traditional covariates. External validation in the eICU database confirmed similar performance. Conclusion: EASIX is a reliable prognostic indicator for short-term mortality in SA-AKI patients. Elevated EASIX levels are associated with increased mortality risk. Future research should explore its clinical utility in risk stratification for SA-AKI.