Association between S100 calcium-binding protein A12 and sepsis associated-acute kidney injury: a prospective cohort study

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, yet early diagnostic biomarkers remain limited. S100A12, a pro-inflammatory calcium-binding protein, may contribute to sepsis-induced renal injury through oxidative and immune-mediated mechanisms. This study aimed to investigate the association between plasma S100A12 levels and the risk of SA-AKI in a prospective sepsis cohort. METHODS: In this prospective cohort study, 202 adult patients with sepsis were consecutively enrolled. Plasma S100A12 levels were measured at enrollment. Associations between S100A12 (continuous and tertiles) and SA-AKI were assessed using multivariable logistic regression (Models 1–3) with progressive adjustment for clinical and laboratory covariates. Restricted cubic spline (RCS) regression and Cox proportional-hazards models were applied to evaluate dose–response and temporal relationships. Predictive performance was assessed using receiver-operating characteristic (ROC) analysis. RESULTS: SA-AKI occurred in 59.9% of participants. S100A12 concentrations were positively associated with SA-AKI risk. After adjustment for confounders, elevated S100A12 was independently associated with SA-AKI (odds ratio 1.17, 95% CI 1.11–1.24, p < 0.001). No significant interactions were observed across predefined subgroups (all p for interaction > 0.05). The area under the ROC curve (AUC) was 0.839 (95% CI 0.783–0.895). CONCLUSIONS: Higher plasma S100A12 levels were independently associated with the development of sepsis-associated acute kidney injury in critically ill patients with sepsis. S100A12 may represent a candidate biomarker for early risk stratification in SA-AKI; however, external validation in larger, multicenter cohorts is required before any potential clinical application. TRIAL REGISTRATION: This prospective observational study was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2400094790) on December 27, 2024, after ethics approval, as no interventional procedures were performed.