Circulating Angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case-cohort study

Angiopoietin 2 (Angpt2) impairs endothelial function by preventing angiopoietin 1 from binding to their common endothelial-specific receptor Tie2. Here, we examined whether circulating Angpt2 predicts outcome in kidney transplant recipients. For this case-cohort study, we selected 130 kidney transplant recipients who had died or returned to dialysis within the first 2years of follow-up of our cohort study, as well as 130 age- and gender-matched kidney transplant recipients without an event (controls) from a total of 993 kidney transplant recipients. The total of 260 selected patients were followed in median 4years. Serum Angpt2 at baseline was measured using an in-house immunoluminometric assay. Median Angpt2 concentrations were significantly higher in patients who died [median (interquartile range - IQR) 3.6 (2.8-5.9)ng/ml] as compared to patients who did not die during the study period [2.8 (2.1-4.1)ng/ml; P<0.001]. Ln (natural log) Angpt2 levels correlated positively with C-reactive protein levels (r=0.315, P<0.001) and the Charlson Comorbidity Index (r=0.188, P=0.002) and were inversely associated with eGFR (r=-0.301, P<0.001) hemoglobin (r=-0.269, P<0.001), and serum albumin concentrations (r=-0.382, P<0.001). On multivariate analyses, baseline Angpt2 levels independently predicted all-cause mortality (multivariable-adjusted hazard ratio associated with one natural log unit higher Angpt2 level: 1.70 (95% confidence interval: 1.10-2.61)). In our analysis, circulating Angpt2 was an independent predictor of all-cause mortality in stable, prevalent kidney transplant recipients.