Purpose: Endostatin is a promising biomarker for predicting acute kidney injury (AKI) and mortality in the intensive care unit (ICU). We investigated plasma endostatin upon ICU admission as a predictor of AKI, renal replacement therapy (RRT), and 30-day mortality. Methods: A retrospective multicenter study was performed with admissions (ICU length of stay ≥24 hours) to four ICUs. KDIGO criteria defined AKI. Endostatin on ICU admission was compared to creatinine, cystatin C, and the Simplified Acute Physiology Score 3 (SAPS-3). Admissions with sepsis and creatinine <100 μmol/L on ICU admission underwent subgroup analyses. Regression models and the area under the receiver operating characteristic curve (AUC) were assessed. Results: In total, 4449 admissions were included (43% sepsis and 61% AKI). Endostatin was associated with AKI (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.7), future AKI (OR 1.5, 95% CI 1.4-1.7), future AKI stage 3 (OR 1.4, 95% CI 1.2-1.6), and RRT (OR 1.2, 95% CI 1.1-1.4) independently of creatinine and cystatin C, with similar results in sepsis. Endostatin was also associated with time to AKI (hazard ratio 1.2, 95% CI 1.1-1.2). For admissions with creatinine <100 μmol/L, endostatin (AUC 0.62, 95% CI 0.59-0.65) outperformed creatinine (AUC 0.51, 95% CI 0.49-0.54) and cystatin C (AUC 0.53, 95% CI 0.50-0.56) in predicting future AKI (p<0.001). Endostatin was not associated with 30-day mortality after adjusting for SAPS-3. Conclusion: Endostatin is an early and potentially clinically useful biomarker for predicting AKI and RRT needs at ICU admission, especially in patients with low to mildly elevated creatinine.

The authors have declared no competing interest.

HK and JE were funded by Kristianstad Hospital, Department of Anaesthesia and Intensive Care. AF was funded by: Regional research support, Region Skane #2022-1284; Governmental funding of clinical research within the Swedish National Health Service (ALF) #2022:YF0009 and #2022-0075; Crafoord Foundation grant number #2021-0833; Lions Skane research grants; Skane University Hospital grants; Swedish Heart and Lund Foundation (HLF) #2022-0352 and #2022-0458. The funding organisations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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This study was approved by the regional ethical review board in Lund, Sweden (DNR 2015/267 and 2017/802).

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The datasets generated and analysed during the current study are not publicly available due to limitations in the ethical approval of the study and data management policies of Region Skane. However, they are available from the corresponding author on request.