Angiopoietin/Tie2 Dysbalance Is Associated with Acute Kidney Injury after Cardiac Surgery Assisted by Cardiopulmonary Bypass

• Published in: PloS one 2015-08, Vol.10 (8), p.e0136205-e0136205
• Main Authors: Jongman, Rianne M, van Klarenbosch, Jan, Molema, Grietje, Zijlstra, Jan G, de Vries, Adrianus J, van Meurs, Matijs
• Format: Article
• Language: English
• Subjects: Acetylglucosaminidase - urine; Acute Kidney Injury - physiopathology; Aged; Albuminuria - urine; Anesthesiology; Angiopoietin; Angiopoietin-1 - blood; Angiopoietin-1 - metabolism; Angiopoietin-2 - blood; Biology; Biomarkers - blood; Cardiac Surgical Procedures - adverse effects; Cardiopulmonary bypass; Cardiopulmonary Bypass - adverse effects; Creatinine; Creatinine - blood; Critical care; Cytokines; Endothelium; Female; Glucosaminidase; Health aspects; Heart; Heart diseases; Heart surgery; Hepatitis A Virus Cellular Receptor 1; Humans; Inflammation; Injuries; Kidney diseases; Kidneys; Male; Membrane Glycoproteins - urine; Molecular chains; Mortality; Pathology; Patients; Physiological aspects; Plasma levels; Prospective Studies; Receptor, TIE-2 - blood; Receptor, TIE-2 - metabolism; Receptors, Virus; Risk factors; Sepsis; Surgery; TNF inhibitors; Tumor necrosis factor-TNF; Urine; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136205

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. 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. 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. The endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients.