Angiopoietin-2 and Mortality Outcomes in End-Stage Renal Disease with Heart Failure as a Comorbidity

Abstract

Angiopoeitin-2 (Ang2) is a vascular growth factor involved in regulating angiogenesis and endothelial remodeling. Higher Ang2 levels have been associated with mortality in the general population and among male hemodialysis patients, but its effects on concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) are unknown. Plasma samples from 73 ESRD patients and 40 healthy patients were analyzed for Ang2 concentrations using ELISA. Patient groups were stratified into those with or without HFrEF (EF < 50%). At two years following sample collection, the medical record was reviewed for mortality. The optimal cut-off value for Ang2 to predict all-cause mortality was 1671 pg/mL (AUC 0.73, sensitivity 0.714, specificity 0.750) based on the regression analysis. Statistical analyses included Mann–Whitney U tests, Cox proportional hazards model, and Log-rank test. Multiple comorbidities were present; coronary artery disease 46%, diabetes 69%, hypertension 97%, and smoking 49%. Patients with one- and two-year mortality had higher Ang2. Ang2 levels above the optimal cut-off are associated with mortality within the entire ESRD sample and within the group with both ESRD and HFrEF. In the Cox proportional hazards analysis, Ang2 levels were associated with mortality within the larger ESRD sample but not in the group with ESRD and HFrEF. Ang2 has potential as a non-specific biomarker for prognostication in patients with cardiorenal syndrome given its association with mortality, despite modest sex-based differences. Future research should be conducted with larger samples to evaluate if it has prognostic value in individuals with HFrEF and ESRD of varying severity and temporality.