hfe mutations modulate the effect of iron on serum hepcidin25 in chronic hemodialysis patients background and objectives increased serum hepcidin has been reported in patients receiving chronic hemodialysis and hypothesized to contribute to the alterations of iron metabolism of endstage renal disease however no quantitative assessment is available to date the clinical determinants are still under definition and the role of genetic factors namely hfe mutations has not yet been evaluated the aim of this study was to quantitatively assess serum hepcidin25 in hemodialysis patients versus controls and analyze the relationship between hepcidin iron indices hfe genotype and erythropoietic parametersdesign setting participants measurements sixtyfive hemodialysis patients and 57 healthy controls were considered hepcidin25 was evaluated by surfaceenhanced laser desorptionionization timeofflight mass spectrometry hfe genotype by restriction analysisresults serum hepcidin25 was higher in hemodialysis patients compared with controls in patients hepcidin25 correlated positively with ferritin and c reactive protein and negatively with serum iron after adjustment for confounders hepcidinferritin ratio was lower in patients with n 25 than in those without n 40 hfe mutations at multivariate analysis hepcidin25 was independently associated with ferritin and hfe status in a subgroup of 22 stable patients ie with hb levels on target normal crp levels and absence of complications for at least 1 yr hepcidin25 was negatively correlated with hb levels independently of confoundersconclusions serum hepcidin25 is increased in hemodialysis patients regulated by iron stores and inflammation and relatively reduced in subjects carrying frequent hfe mutations hepcidin25 may contribute to the pathogenesis of anemia by decreasing iron availability