Abstract
IntroductionThe 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.MethodsFrom 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.ResultsAng2 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.ConclusionsThe endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients.
Highlights
The pathophysiology of acute kidney injury (AKI) after cardiac surgery is not completely understood
Ang2 levels increased 1.7-fold more in patients who developed AKI after cardiac surgery compared to matched control patients
The endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients
Summary
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). Systemic levels of Ang, Ang, and sTie were measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1) and N-acetyl-betaD-glucosaminidase (NAG) were measured in the urine This observational study consisted of 541 patients, a subgroup of a larger randomized prospective multicenter clinical trial that investigated the effects of intraoperative cell salvage and leukocyte depletion on allogeneic blood exposure during cardiac surgery. Procedure related variables were entered into the model These matched control pairs were created using a macro for SPSS (Version 18.0, IBM Chicago, Ill.), which compared the nearest propensity scores of the patients without AKI with the scores of the patients with AKI. The standardized difference between the groups were calculated to assess the imbalance of covariates (Table 1)
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