Greater potency of darbepoetin-α than erythropoietin in suppression of serum hepcidin-25 and utilization of iron for erythropoiesis in hemodialysis patients

Background The potency of darbepoetin- (DPO-) to improve anemia in hemodialysis (HD) patients is greater than that of recombinant human erythropoietin (rHuEPO). Design and methods To assess the potency of DPO- to mobilize iron from body stores in comparison with rHuEPO in HD patients without apparent inflammation or infection, serum iron, transferrin saturation (TSAT), ferritin, and hepcidin-25 were measured serially. This study included (i) a long-term crossover study for 3yr to compare the effects of the two erythropoiesis-stimulating agents (ESA) on serum iron, TSAT, and ferritin, and (ii) a short-term crossover study for 8wk to examine their effects on serum hepcidin-25 in HD patients. Results The long-term crossover study demonstrated that the change of ESA from rHuEPO to DPO- significantly decreased serum ferritin while serum iron and TSAT remained unchanged, while DPO- as well as rHuEPO maintained hemoglobin level in the target range between 10.0 and 11.0g/dL. Furthermore, in the short-term crossover study, area under the percent suppression of serum hepcidin-25 time curve for the first 7d during the DPO- treatment period was significantly greater than that during the rHuEPO period (348.0 +/- 92.4 vs. 178.4 +/- 131.5%.day P=0.030). The greater suppression of hepcidin-25 by DPO- may facilitate iron mobilization, resulting in diminution of body iron stores without any significant effect on serum iron utilizable for erythropoiesis. Conclusion This study demonstrated that DPO- has a greater advantage than rHuEPO in that it facilitates iron mobilization from body stores into bone marrow to induce effective erythropoiesis and thus could protect against possible harmful effects caused by excessive iron stores in the body.