Determinants of Hepcidin in Patients on Maintenance Hemodialysis: Role of Inflammation

Abstract

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.

Serum Hepcidin in Haemodialysis Patients: Associations with Iron Status and Microinflammation

“…In contrast, no relationship was observed between hepcidin and hsCRP levels, or between hepcidin levels and EPO (ESA) dose, which is consistent with previous studies. 12 Several factors may explain this lack of relationship, including differences in the half-lives of hsCRP and hepcidin. 22,23 Another explanation may be the distinct features of the study population, 20 Previous studies have shown that comparison between hepcidin and hsCRP may serve as a quick and easy method for identifying the difference between iron deficiency, microinflammation or mixed anaemia.…”

“…The ESA resistance index (ERI) was calculated as the ratio of the weekly EPO dose to Hb per unit weight. 12 The single-pool urea clearance index was used to represent weekly dialysis dose and was calculated as K t /V, where K is the clearance of urea by the dialyser, t is the dialysis time and V is the volume of distribution of urea. …”

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…It has been suggested that the serum hepcidin levels of CKD patients are higher compared with those of healthy individuals. However, a recent study revealed that the serum hepcidin levels of all HD patients were not necessarily significantly higher compared with those of healthy individuals and that the serum hepcidin levels in 46% of HD patients were within the healthy range [161]. Thus, it is possible that in HD patients with small liver iron stores, the hepcidin level is low and the absorption of iron through the digestive tract may not be inhibited.…”

Hepcidin in Human Iron Disorders: Diagnostic Implications

“…Hepcidin in CKD also has been associated with iron-restricted erythropoiesis, as reflected by the relation of hepcidin with lower hemoglobin and/or reticulocyte counts (31,169,171 ). Furthermore, CRP and IL-6 were shown to be less relevant predictors in the setting of renal insufficiency (16,170,(172)(173)(174)(175). Intravenous iron administration was found not to influence hepcidin concentrations in hemodialysis (HD) patients that were withheld from iron and ESA therapy for 2 weeks (169 ), whereas it increased hepcidin in iron-naïve CKD patients (31,96 ).…”