Effects of the route of erythropoietin administration on hemoglobin variability and cardiovascular events in hemodialysis patients

INTRODUCTION: Despite of the routine use of erythropoietin in hemodialysis patients to correct anemia, its administration route’s effects on hemoglobin variability and cardiovascular events remain elusive. Herein, we determined different erythropoietin administration routes’ effects on hemoglobin variability in hemodialysis patients and the associated factors of hemoglobin variability and cardiovascular events. METHODS: This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of <25%. RESULTS: In this analysis, 37 patients (51.1%) were male, and the mean age was 50.6 ± 12.5 years. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high group was a significant independent risk factor for cardiovascular events (p = 0.03). CONCLUSION: The risk out of the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.