The majority of end-stage renal patients undergoing maintenance hemodialysis (HD) develop anemia that adversely affects their quality of life and increases the risk for cardiovascular events and death. Thus, the development of safe and effective strategies aimed at correcting anemia in these patients is of utmost importance. 1 Unfortunately, the response to erythropoietin (EPO) treatment is often suboptimal, due mainly to an imbalance between the surging iron requirements of the stimulated erythropoietic cells on the one hand and iron availability on the other. Thus, intravenous (iv) administration of ironcontaining preparations is widely used in order to circumvent this imbalance. However, questions about the efficacy and the safety of this loading strategy still remain unanswered. 1

Serum protein transferrin represents the physiological iron supplier to body cells requiring iron, mainly the erythroblasts in bone marrow. Transferrin iron is derived mainly from macrophages of the reticuloendothelial system (RES), following degradation of senescent erythrocytes and subsequent efflux of the liberated iron to the circulation. 2 This process, as well as the liberation of iron from duodenal enterocytes and from hepatocytes, is mediated by ferroportin, the only known iron exporter. 3 On the other hand, the expression of ferroportin is negatively regulated by hepcidin, a liver-produced peptide hormone that binds to ferroportin and induces its internalization and degradation, thus blocking iron export and its utilization for erythropoiesis. 3 Hepcidin expression is regulated by a number of different signals, including iron levels, inflammation, rate of erythropoiesis and hypoxia. 4 The exact molecular mechanism (s) of iron-mediated regulation of hepcidin expression is not completely understood. There is substantial evidence to indicate that elevated concentrations of the differic transferrin form (Tf-Fe2) in serum can induce hepcidin expression. This event is likely to be mediated through Tf-Fe2 binding to transferrin receptor 2 (TfR2) on the surface of hepatocytes. 5