Endothelial activation and stress index in risk stratification and treatment optimization for critically ill patients with acute kidney injury: A retrospective cohort study from MIMIC-Ⅳ database

Background Endothelial dysfunction is critical in the pathogenesis of acute kidney injury (AKI). It sought to investigate the role of endothelial activation and stress index (EASIX) in risk stratification and treatment optimization for critically ill patients with AKI. Methods Utilizing MIMIC-Ⅳ 3.1 database, a retrospective cohort study was undertaken. Given the non-normal distribution, EASIX was transformed logarithmically. The endpoints were 1-year and ICU all-cause mortality. The association was assessed using Kaplan-Meier curves, Cox models, restricted cubic splines and propensity score via overlap weights. Subgroup analyses were conducted to assess optimal population for EASIX application and to preliminarily explore its potential role in guiding treatment strategy optimization. Results It comprised 17624 patients with AKI, exhibiting 1-year and ICU mortality rates of 44.6% and 19.2%. Elevated log2(EASIX) levels were independently associated with an increased 1-year mortality (HR: 1.41, 95% CI: 1.32–1.50) and ICU mortality (RR: 1.49, 95% CI: 1.38–1.62), as a finding corroborated by overlap-weighted propensity score analysis. Subgroup analyses indicated a stronger association in patients without severe AKI, CKD, sepsis or CRRT, and patients with lower levels of age or Acute Physiology Score (APS) Ⅲ and higher levels of albumin ( p < 0.05 for all). The glucocorticoid use may be independently associated with an increased risk of 1-year (HR: 1.27, 95% CI: 1.21–1.34) and ICU (HR: 1.39, 95% CI: 1.31–1.47) mortality. The glucocorticoid-associated risk decreased as the log2(EASIX) level increased ( p < 0.001). Conclusion It found the positive association between log2(EASIX) levels and risk of mortality in critically ill patients suffering from AKI, particularly in those with decreased age or APS Ⅲ, elevated albumin, and those characterized by mild AKI, or absence of CKD, sepsis or CRRT. These findings underscored the significance of EASIX in enhancing risk stratification systems and in guiding personalized anti-inflammatory treatment strategies.