title: Angiopoietin/Tie2 Dysbalance Is Associated with Acute Kidney Injury after Cardiac Surgery Assisted by Cardiopulmonary Bypass.
abstract: BACKGROUND
  The pathophysiology of acute kidney injury (AKI) after cardiac surgery is not completely understood. Recent evidence suggests a pivotal role for the endothelium in AKI. In experimental models of AKI, the endothelial specific receptor Tie2 with its ligands Angiopoietin (Ang) 1 and Ang2 are deranged. This study investigates their status after cardiac surgery, and a possible relation between angiopoietins and AKI.
  
  
  METHODS
  From a cohort of 541 patients that underwent cardiac surgery, blood and urine was collected at 5 predefined time points. From this cohort we identified 21 patients who had at least 50% post-operative serum creatinine increase (AKI). We constructed a control group (n = 21) using propensity matching. Systemic levels of Ang1, Ang2, and sTie2 were measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in the urine.
  
  
  RESULTS
  Ang2 plasma levels increased over time in AKI (from 4.2 to 11.6 ng/ml) and control patients (from 3.0 to 6.7 ng/ml). Ang2 levels increased 1.7-fold more in patients who developed AKI after cardiac surgery compared to matched control patients. Plasma levels of sTie2 decreased 1.6-fold and Ang1 decreased 3-fold over time in both groups, but were not different between AKI and controls (Ang1 P = 0.583 and sTie2 P = 0.679). Moreover, we found a positive correlation between plasma levels of Ang2 and urinary levels of NAG.
  
  
  CONCLUSIONS
  The endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients.
authors: Department of Anesthesiology, University Medical Center Groningen, Groningen, the Netherlands; Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, Groningen, the Netherlands; Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands.
authors: Rianne M
authors: RM
authors: Jongman
authors: Department of Anesthesiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Jan
authors: J
authors: van Klarenbosch
authors: Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, Groningen, the Netherlands.
authors: Grietje
authors: G
authors: Molema
authors: Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands.
authors: Jan G
authors: JG
authors: Zijlstra
authors: Department of Anesthesiology, University Medical Center Groningen, Groningen, the Netherlands.
authors: Adrianus J
authors: AJ
authors: de Vries
authors: Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, Groningen, the Netherlands; Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands.
authors: Matijs
authors: M
authors: van Meurs
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000503:physiopathology; D000419:Albuminuria / Q000652:urine; D042683:Angiopoietin-1 / Q000097:blood / Q000378:metabolism; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins / Q000652:urine; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood / Q000378:metabolism; D011991:Receptors, Virus; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D000118:Acetylglucosaminidase; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; D003404:Creatinine; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D042787:Receptor, TIE-2; D011991:Receptors, Virus