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

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. 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. 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). 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. 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.