Investigation of hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in hemodialysis patients

Background: Decreased responsiveness to erythropoiesis stimulating agents (ESAs) in patients undergoing dialysis is related to various causative factors. Its associations with such factors were examined using the erythropoiesis resistance index (ERI) as an indicator of decreased responsiveness to ESAs in dialysis patients. Subjects: Subjects were 130 patients (91 males and 39 females) on maintenance dialysis. Their ages averaged 69±11 (mean±SD) years. The mean history of dialysis was 55±60 months. Methods: We defined ERI as the weekly dose of ESA per body weight divided by hemoglobin (ESA dose/kg/g/dL/week). The ESA dose was calculated in terms of the rHuEPO equivalent, and the average weekly dose of ESAs in the past month was used to examine associations between decreased responsiveness to ESAs and various factors. Results: Decreased responsiveness to ESAs showed a significant negative correlation with the iron metabolism markers Fe, TIBC, and TSAT, whereas a significant positive correlation was noted with ferritin. Hyporesponsiveness showed a significant positive correlation with the inflammatory cytokine IL-6, whereas significant negative correlations were noted with albumin, GNRI, parameters of the nutritional state, and also body weight and BMI. Furthermore, hyporesponsiveness showed a significant negative correlation with fetuin-A, an arteriosclerosis-related parameter, and a positive correlation with baPWV. A significant positive correlation was also observed with the oxidant stress molecule 8-OHdG, while there was a significant negative correlation with the lipid system parameters total cholesterol, LDL-cholesterol, and triglycerides. Multivariate analysis revealed significant correlations between hyporesponsiveness and TSAT, TIBC, BMI, and 8-OHdG. Conclusion：Our results suggest the participation of the iron metabolism markers Fe, TIBC, and TSAT, the inflammatory cytokine IL-6, the nutrition condition-related parameters albumin, GNRI, body weight, and BMI, the arteriosclerosis-related parameters fetuin-A and baPWV, the oxidant stress molecule 8-OHdG, and the lipid system parameters total cholesterol, LDL-cholesterol, and triglycerides in the decreased responsiveness to ESAs.