title: Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, D-30171, Germany. kuempers.philipp@mh-hannover.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukasz
authors.forename: Sascha
authors.initials: S
authors.lastname: David
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horn
authors.forename: Carsten
authors.initials: C
authors.lastname: Hafer
authors.forename: Robert
authors.initials: R
authors.lastname: Faulhaber-Walter
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood*; D003422:Critical Care; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005544:Forecasting; D005858:Germany / Q000453:epidemiology; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D042787:Receptor, TIE-2; D055815:Young Adult
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2