Plasma endostatin and its association with new-onset acute kidney injury in critical care

Abstract

Background: Endostatin is a promising biomarker for predicting acute kidney injury (AKI) and mortality in the intensive care unit (ICU). We investigated plasma endostatin levels at ICU admission as predictors of new-onset AKI within 48 h after ICU admission, renal replacement therapy (RRT) within 7 days after ICU admission, and 30-day mortality. Methods: A retrospective multicentre study was performed with admissions to four ICUs. Blood samples were prospectively obtained at ICU admission and retrospectively analysed. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria defined AKI. Endostatin at ICU admission was compared to and adjusted for creatinine, cystatin C, and the Simplified Acute Physiology Score 3 (SAPS-3). Regression models and mean areas under the receiver operating characteristic curves (AUCs) from repeated cross-validation were assessed. Results: In total, 4732 admissions were included. Endostatin was associated with new-onset AKI (OR 1.7, 95% CI 1.5-1.9), new-onset stage 3 AKI (OR 1.4, 95% CI 1.2-1.6), and RRT (OR 1.2, 95% CI 1.05-1.4) independently of creatinine, cystatin C, and SAPS-3. Endostatin was superior to creatinine and cystatin C in predicting new-onset AKI (mean AUC 0.67 vs. 0.63, p < 0.001). Adding endostatin to creatinine improved the prediction of new-onset AKI and new-onset stage 3 AKI, but not the need for RRT. Endostatin was not associated with 30-day mortality after adjusting for the SAPS-3 score. Conclusions: Endostatin at ICU admission is an independent predictor of new-onset AKI and may improve early AKI risk assessment in the ICU. However, its predictive value for RRT and 30-day mortality appears limited. External validation and studies on its clinical utility are warranted.