Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome

Endothelial activation has emerged as an early event in the pathogenesis of microcirculatory dysfunction, capillary leakage and multi-organ dysfunction syndrome (MODS). Angiopoietin-2 (Ang-2), a circulating antagonistic ligand of the endothelial-specific Tie2 receptor, has been identified as a non-redundant gatekeeper of endothelial activation. On the basis of our previous report demonstrating release of Ang-2 in endotoxemia and sepsis, we aimed to study the utility of Ang-2 to serve as an outcome-specific biomarker in patients requiring renal replacement therapy (RRT) in the intensive care unit (ICU). We measured circulating Ang-2 by ELISA in 117 critically ill patients with AKI at inception of RRT in the ICU. Mortality, length of stay and renal recovery were prospectively assessed during a study period of 28 days after the inception of RRT. Circulating Ang-2 levels were significantly higher in AKI patients with RIFLE category-Injury or -Failure, compared to patients with RIFLE category-Risk. Elevated levels of circulating Ang-2 correlated with impaired oxygenation, low mean arterial pressure, vasopressor dose and the sequential organ failure assessment (SOFA) score. Ang-2 concentrations were significantly higher in non-survivors than in survivors at day 0 and day 14 after initiation of RRT. Multivariate Cox regression and decision tree analyses confirmed a strong independent prognostic impact of elevated Ang-2 as a predictor of 28-day survival. The results from this study indicate that circulating Ang-2 is as a strong and independent predictor of mortality in ICU patients with dialysis-dependent AKI.