Plasma interleukin-1 receptor antagonist in pediatric patients as a potential biomarker for sepsis-associated acute kidney injury: a cohort study

Abstract

Our goal is to evaluate the potential of interleukin-1 receptor antagonist (IL-1Ra) as a biomarker for sepsis-associated acute kidney injury (SA-AKI). Specifically, we aim to explore the correlation between acutely elevated endogenous IL-1Ra and SA-AKI, and to identify the potential time window for its use as a candidate marker. We conducted a prospective cohort study between May 2022 and January 2025. We applied latent class trajectory models (LCTM) to explore different IL-1Ra level trajectories over time, identifying distinct subpopulations, along with a potential time window for its application. We used Spearman’s correlation and logistic regression analysis to examine the relationship between Day 1 IL-1Ra levels and SA-AKI. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) with internal bootstrap validation. The study included 158 pediatric patients, of whom 44 developed SA-AKI within seven days of admission, while 114 did not develop SA-AKI. The trajectory model revealed that the potential monitoring window for IL-1Ra assessment occurs within three days in the PICU for sepsis and identified two distinct subpopulations, with the U-shape group showing more severe disease at admission and a higher 90-day mortality proportion. Logistic regression results showed that IL-1Ra levels were positively correlated with SA-AKI (OR = 1.51, 95% CI: 1.23–1.88, p = 0.0001), particularly with early SA-AKI (OR = 1.61, 95% CI: 1.29–2.05, p < 0.0001). The potential time window for IL-1Ra monitoring appears to be in the early stages of sepsis. Patients with a U-shape change in IL-1Ra exhibit more severe disease and worse outcomes. Plasma IL-1Ra levels on the first day of PICU admission are positively correlated with the occurrence of SA-AKI, especially early SA-AKI. Our findings support further evaluation of IL-1Ra as a candidate early risk marker for SA-AKI.