Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome.
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.
Kümpers
Philipp
P
Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. kuempers.philipp@mh-hannover.de
Hafer
Carsten
C
David
Sascha
S
Hecker
Hartmut
H
Lukasz
Alexander
A
Fliser
Danilo
D
Haller
Hermann
H
Kielstein
Jan T
JT
Faulhaber-Walter
Robert
R
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
D042702:Angiopoietin-2; D015415:Biomarkers