Serum pro-hepcidin level and iron homeostasis in Japanese dialysis patients with erythropoietin (EPO)-resistant anemia.

BACKGROUND Resistance to EPO therapy in hemodialysis (HD) patients is ascribed to inflammation and iron deficiency. Hepcidin, an antimicrobial peptide, is a key regulator of iron metabolism and synthesis of hepcidin is regulated by iron status and inflammation. The role of hepcidin in the pathogenesis of EPO-resistant anemia was assessed through measurement of serum pro-hepcidin in HD patients. MATERIAL/METHODS Serum pro-hepcidin was measured by ELISA in 57 HD patients, who were divided into three groups: Group I (n=19) had EPO-resistance anemia, based on serum ferritin of > or =100 ng/ml and EPO dose (9,000 IU/week maximum dose for 6 months); Group II (n=19) had iron-deficiency anemia, based on serum ferritin of <100 ng/ml and/or <20% transferrin iron saturation (TSAT); and Group III (n=19) had no iron deficiency and anemia. Nineteen age- and sex-matched healthy volunteers were enrolled as controls (Group IV). RESULTS Serum pro-hepcidin was significantly lower in Group II than in other groups. In Group I, serum pro-hepcidin did not differ significantly from controls. Serum levels of ferritin, hs-CRP and IL-6 were higher in Group I than in other groups, and serum sTfR was higher in Groups I and II than in controls. CONCLUSIONS In EPO resistant anemia, multiple factors, including iron and inflammation related conditions, are likely to affect the level of hepcidin and this may explain the lack of elevated serum hepcidin in this condition.