Effect of Route of EPO Administration on Hemodialysis Arteriovenous Vascular Access Failure: A Randomized Controlled Trial

Abstract

Vascular access failure is a major cause of morbidity and hospitalization in hemodialysis populations worldwide. Erythropoietin (EPO) potentially can contribute to vascular access stenosis and occlusion by promoting intimal hyperplasia and thrombosis. Intravenous administration of EPO results in a severe, but transient, increase in drug concentration within the vascular access, whereas subcutaneous administration leads to a mild, but sustained, increase in the systemic circulation. The effect of route of administration of EPO on vascular access outcomes is uncertain. Randomized controlled trial. 78 Korean hemodialysis patients were randomly assigned to receive either intravenous (n = 40) or subcutaneous (n = 38) EPO. EPO was administered during dialysis, and the dose was titrated to maintain hemoglobin levels between 9 to 12 g/dL. All patients received EPO 2 or 3 times/wk. Study duration was 4 to 77 months. The primary end point was time to vascular access failure. Analysis was performed using Cox regression analysis. The incidence of access failure was 4.7%/patient-year in the intravenous-therapy group and 12.0%/patient-year in the subcutaneous-therapy group, with an unadjusted hazard ratio of 3.24 (95% confidence interval, 1.31 to 8.00; P = 0.01). After adjustment for dialysis access type, vascular access age, previous intervention, serum phosphorus level, and diabetes mellitus, subcutaneous EPO administration was independently associated with increased vascular access failure (hazard ratio, 3.56; 95% confidence interval, 1.20 to 10.58; P = 0.02). There were no significant differences in either hemoglobin concentration or EPO dosage between the 2 groups during the study period. Relatively small sample size and lack of complete symmetry between the 2 groups with respect to some baseline characteristics. This study suggests that the risk of vascular access failure may be greater with subcutaneous compared with intravenous administration of EPO in hemodialysis patients.