title: Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. kuempers.philipp@mh-hannover.de
authors: Philipp
authors: P
authors: Kümpers
authors: Carsten
authors: C
authors: Hafer
authors: Sascha
authors: S
authors: David
authors: Hartmut
authors: H
authors: Hecker
authors: Alexander
authors: A
authors: Lukasz
authors: Danilo
authors: D
authors: Fliser
authors: Hermann
authors: H
authors: Haller
authors: Jan T
authors: JT
authors: Kielstein
authors: Robert
authors: R
authors: Faulhaber-Walter
mesh_terms: D058186:Acute Kidney Injury / Q000145:classification / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005858:Germany / Q000453:epidemiology; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D017063:Outcome Assessment, Health Care / Q000379:methods*; D016016:Proportional Hazards Models; D012372:ROC Curve; D017582:Renal Replacement Therapy
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers