Angiopoietin-2 predicts all-cause mortality in male but not female end-stage kidney disease patients on hemodialysis.

BACKGROUND Angiopoietin-2 (Ang-2) plays a pivotal role in pathological vascular remodeling and angiogenesis. Both vascular mechanisms are active in patients with end-stage renal disease (ESRD) and may contribute to the high mortality in these patients. The aim of this multicenter prospective cohort study was to investigate baseline serum Ang-2 concentrations in ESRD patients on hemodialysis (HD) for their ability to predict all-cause mortality. METHODS We conducted a prospective cohort study in 340 stable HD patients from different chronic dialysis centers in Berlin, Germany. The primary endpoint was all-cause mortality during a 5-year follow-up period. Blood samples and clinical data were collected at baseline. Serum Ang-2 was measured with a validated ELISA (Biomedica). RESULTS 313 HD patients (206 men and 107 women) were finally included into the study. ROC analysis of Ang-2 concentrations yielded an AUC of 0.65 (p <0.0001) for predicting all-cause mortality in the entire study population and was used to determine the optimal cut-off (111.0 pmol/l) for all-cause mortality. Kaplan-Meier survival analysis indicated that male but not female end-stage kidney disease patients on hemodialysis with higher Ang-2 concentrations had a significantly lower survival (log-rank test, p< 0.0001 and P = 0.249 for male and female, respectively). Multivariable Cox regression analyses adjusted for age, comorbidity, smoking, dialysis vintage, serum creatinine, hemoglobin, C-reactive protein, serum albumin, iPTH, LDL, and Kt/V likewise indicated that elevated Ang-2 concentrations are associated with all-cause mortality in male (HR, 3.294, 95% CI, 1.768-6.138, p = 0.0002), but not in female end-stage kidney disease patients on hemodialysis (HR, 1.084, 95% CI, 0.476-2.467, p = 0.847). CONCLUSION Ang-2 at baseline is independently associated with all-cause mortality in male ESRD patients on HD.