Research

Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients

Philipp Kümpers¹ , Alexander Lukasz¹ , Sascha David¹ , Rüdiger Horn² , Carsten Hafer¹ , Robert Faulhaber-Walter¹ , Danilo Fliser³ , Hermann Haller¹ and Jan T Kielstein¹

¹  Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, D-30171, Germany

²  Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, D-30171, Germany

³  Renal and Hypertensive Diseases, Saarland University Medical Centre, Kirrberger Straße, D-66421, Homburg/Saar, Germany

author email corresponding author email

Critical Care 2008, 12:R147doi:10.1186/cc7130

Published:	21 November 2008

See related commentary by Giuliano Jr and Wheeler, http://ccforum.com/content/13/1/114

Abstract

Introduction

The endothelial specific angiopoietin (Ang)-Tie2 ligand-receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis. Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage, whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function. Here, we examine whether circulating Ang-1 and/or Ang-2 independently predict mortality in a cohort of critically ill medical patients.

Methods

Circulating vascular endothelial growth factor (VEGF), Ang-1 and Ang-2 were prospectively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay (IRMA) and ELISA, respectively. Survival after 30 days was the primary outcome studied.

Results

Median serum Ang-2 concentrations were increasingly higher across the following groups: healthy controls, patients without sepsis, patients with sepsis and patients with septic shock. In contrast, Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls. Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO₂)/fraction of inspired oxygen (FiO₂), tissue hypoxia, Sequential Organ Failure Assessment (SOFA) and Physiology and Chronic Health Evaluation II (APACHE II) score. Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival.

Conclusions

A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients. Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness. Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU.