Osteopontin predicts survival in critically ill patients with acute kidney injury

Abstract

The cytokine osteopontin is involved in the pathophysiology of experimental acute kidney injury. We have tested the hypothesis that osteopontin levels might serve as a biomarker predicting outcome in critically ill patients requiring renal replacement therapy after acute kidney injury. We measured circulating plasma osteopontin levels in 109 critically ill patients with acute kidney injury at inception of renal replacement therapy and 4 weeks thereafter. Critically ill patients without acute kidney injury served as controls. Osteopontin was measured with ELISA. Baseline osteopontin levels in patients with acute kidney injury were significantly higher compared with controls (P<0.0001). Baseline osteopontin levels in patients recovering from acute kidney injury were significantly elevated compared with patients with permanent loss of kidney function after acute kidney injury (P=0.01). In addition, in patients recovering from acute kidney injury without further need for renal replacement therapy, osteopontin levels were significantly lower 4 weeks after initiation of renal replacement therapy (P=0.0005). Moreover, multivariate Cox analysis revealed osteopontin levels at renal replacement therapy inception as an independent and powerful predictor of mortality (P<0.0001). In the ROC-curve analysis, an osteopontin cut-off value of 577 ng/mL separated survivors from non-survivors with a sensitivity of 100% and a specificity of 61% (AUC 0.82; 95% confidence interval: 0.74-0.89; P<0.0001). Osteopontin may serve as a novel biomarker for both, overall survival and renal outcome in critically ill patients with acute kidney injury, that require renal replacement therapy.