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

**Authors:** Huanqin Liu, Mengjia Yu, Yumei Mao, Qingjie Xue, Yanan Lv, Feng Qu, Jikui Shi

PMC · DOI: 10.1186/s12882-026-04760-0 · BMC Nephrology · 2026-01-22

## TL;DR

High levels of a protein called S100A12 are linked to a higher risk of kidney injury in sepsis patients, suggesting it could be a useful early warning sign.

## Contribution

This study identifies S100A12 as a novel potential biomarker for predicting sepsis-associated acute kidney injury.

## Key findings

- Elevated plasma S100A12 levels were independently associated with sepsis-associated acute kidney injury (SA-AKI) after adjusting for confounders.
- The area under the ROC curve for S100A12 in predicting SA-AKI was 0.839, indicating strong predictive performance.

## Abstract

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.

The online version contains supplementary material available at 10.1186/s12882-026-04760-0.

## Linked entities

- **Genes:** S100A12 (S100 calcium binding protein A12) [NCBI Gene 6283]
- **Diseases:** acute kidney injury (MONDO:0002492)

## Full-text entities

- **Genes:** S100A12 (S100 calcium binding protein A12) [NCBI Gene 6283] {aka CAAF1, CAGC, CGRP, ENRAGE, MRP-6, MRP6}
- **Diseases:** acute kidney injury (MESH:D058186), sepsis (MESH:D018805)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12911131