Background/Aim: Hepcidin could be one of the most important regulators for iron metabolism in patients on maintenance hemodialysis (MHD). The factors affecting serum hepcidin levels were evaluated among indexes of anemia, iron metabolism, or inflammation, as well as the dose of erythropoietin. Methods: 198 MHD patients treated with recombinant human erythropoietin were recruited and serum hepcidin-25 levels were specifically measured by liquid chromatography tandem mass spectrometry. Results: In multivariate analysis, only transferrin and ferritin were selected as significant predictors of hepcidin in all patients. In the selected patients with highly sensitive C-reactive protein of >0.3 mg/dl, however, ferritin as well as the IL-6 level were found to be significant predictors for serum hepcidin. The serum ferritin/hepcidin ratio was very similar among MHD and healthy volunteers, suggesting that uremic conditions do not affect the ratio. Serum hepcidin levels decreased by only 27% after a single hemodialysis session, but returned to basal levels 1 h after and remained so until the next hemodialysis session. Conclusions: In the absence of apparent inflammation, the serum hepcidin level could be exclusively associated with ferritin in MHD patients and was independent of inflammatory cytokines. Only in the presence of microinflammation, however, might IL-6 also affect hepcidin expression.

Background. Dysregulated iron metabolism has been suspected to be linked to anemia of chronic disease and to cardiovascular disease (CVD). For the purpose of clarifying the factors affecting arterial stiffness, we evaluated the relationship between iron metabolism, brachial-ankle (ba)-pulse wave velocity (PWV) and several risk factors for CVD in maintenance hemodialysis (MHD) patients. Methods. A total of 168 MHD patients were recruited, and the levels of iron parameters, hepcidin, CVD risk factors and ba-PWV were evaluated. The level of serum hepcidin-25 was specifically measured by liquid chromatography–tandem mass spectrometry. Results. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and hepcidin were higher in MHD patients, which was consistent with results from our previous study. ba-PWV significantly correlated with age (P < 0.01, R = 0.34), total cholesterol (T-CHO; P = 0.02, R = 0.21), TNF-α (P < 0.01, R = 0.24) and hepcidin (P < 0.01, R = 0.25) but not with other iron parameters and CVD risk factors. According to multiple regression analysis, age ( β = 0.30), T-CHO ( β = 0.24) TNF-α ( β = 0.19) and hepcidin ( β = 0.23) were selected as the significant predictors of ba-PWV in MHD patients. Conclusion. Serum levels of both hepcidin and TNF-α are independently associated with arterial stiffness in MHD patients, suggesting that microinflammation and iron metabolism might affect the integrity of arterial walls.

Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (≥100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low β2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term.