The CD4/CD8 ratio as an immune phenotype improves risk stratification for sepsis-associated acute kidney injury: A single-center, multi-ICU Chinese cohort study

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, yet current risk stratification lacks immune-specific biomarkers. The CD4/CD8 T cell ratio, a key indicator of immune homeostasis, has shown prognostic value in sepsis, but its specific association with, and incremental value for predicting, SA-AKI risk in Chinese ICU populations remains underexplored. METHODS: In this single-center, multi-ICU retrospective cohort study, 349 adult septic patients were enrolled. The peripheral blood CD4/CD8 T-cell ratio was measured by flow cytometry within 24 h of ICU admission. Nonlinear associations were assessed using restricted cubic spline (RCS) analysis. Model performance was evaluated by area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Robustness was further assessed through sensitivity and subgroup analyses. RESULTS: A U-shaped relationship was observed between the CD4/CD8 ratio and SA-AKI risk, with the lowest risk at ratios of 1.5-2.5. The CD4/CD8-enhanced model significantly improved predictive performance compared to the clinical model alone (AUC: 0.788 vs. 0.738). Significant improvements in risk reclassification were confirmed by NRI (0.57, 95% CI: 0.40-0.74) and IDI (0.06, 95% CI: 0.03-0.09). DCA demonstrated superior clinical utility across a wide range of risk thresholds. CONCLUSIONS: This study establishes a U-shaped association between the CD4/CD8 ratio and SA-AKI risk, with the nadir of risk at a ratio of 1.5-2.5. These findings support integrating this readily available immune biomarker into risk stratification models to improve early identification of septic patients at high risk for AKI.