Abstract
Hepcidin is a peptide hormone produced by the liver and appears to be the master regulator of iron homeostasis. This peptide is upregulated in inflammatory conditions, including uremia. Hepcidin functions to regulate (inhibit) iron transport across the gut mucosa, thereby preventing excess iron absorption and maintaining normal iron levels within the body. In this study, we aimed to investigate hepcidin levels and their relationship with the parameters of iron status, inflammation, anemia therapy, and parameters of dialysis efficiency in hemodialysis patients. Plasma hepcidin-25, inflammatory markers (high-sensitivity C-reactive protein and interleukin 6), and peripheral iron indices (serum iron, total iron-binding capacity, transferrin saturation and serum ferritin) were measured before hemodialysis in 40 end-stage renal disease (ESRD) patients treated with regular hemodialysis in a single dialysis unit as well as in 20 healthy individuals matched for age and sex serving as the control group. Plasma levels of hepcidin-25 were significantly higher in hemodialysis patients compared with controls. In a simple correlation analysis, plasma hepcidin levels were positively correlated with ferritin, transferrin saturation, CRP, and interleukin 6; however, it was negatively correlated with hemoglobin, dose of epoitin-α, and dose of iron. Serum hepcidin levels were associated with iron status and inflammation in maintenance hemodialysis patients, and the high hepcidin serum levels, found in hemodialysis (HD) patients, are dependent on the magnitude of the inflammatory process and on recombinant human erythropoietin doses. Hepcidin and its regulatory pathways are potential therapeutic targets, which could lead to effective treatment of anemia in chronic hemodialysis.
Highlights
Anemia is a common complication in maintenance hemodialysis patients and contributes to reduced quality of life [1]
In a simple correlation analysis, plasma hepcidin levels were positively correlated with ferritin, transferrin saturation, CRP, and interleukin 6; it was negatively correlated with hemoglobin, dose of epoitin-a, and dose of iron
Serum hepcidin levels were associated with iron status and inflammation in maintenance hemodialysis patients, and the high hepcidin serum levels, found in hemodialysis (HD) patients, are dependent on the magnitude of the inflammatory process and on recombinant human erythropoietin doses
Summary
Anemia is a common complication in maintenance hemodialysis patients and contributes to reduced quality of life [1]. Despite the great success of recombinant human erythropoietin (EPO) in clinical practice for the treatment of anemia in dialysis patients [chronic kidney disease (CKD) patients], resistance to this therapy is ∼10–20% [2,3]. In addition to its antimicrobial properties [5], it is the master regulator of iron metabolism, controlling the amount of dietary iron absorbed from the duodenum and the release of iron from cells in the reticuloendothelial system (Kupffer cells, splenic macrophages, etc.) [6,7,8]. The key role of hepcidin in iron homeostasis and its disorders suggests that its assay in blood or urine could prove useful for the diagnosis and monitoring of iron disorders, and potentially be used as a clinical marker to optimize treatment approaches [10,11]
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