title: Circulating Angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case-cohort study.
abstract: 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 2 years 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 4 years. 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.
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA, USA; Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
authors.forename: Maria E
authors.initials: ME
authors.lastname: Czira
authors.forename: Akos
authors.initials: A
authors.lastname: Ujszaszi
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.forename: Istvan
authors.initials: I
authors.lastname: Mucsi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D002097:C-Reactive Protein
keywords: circulating Angiopoietin 2 level; endothelial dysfunction; kidney transplantation; mortality