title: Hepcidin is a potential regulator of iron status in chronic kidney disease.
abstract: Hepcidin is a small defensin-like peptide produced primarily by hepatocytes, but also by other cells, including macrophages. In addition to hepcidin's antimicrobial properties, it is the main regulator of iron metabolism and controls both the amount of dietary iron absorbed in the duodenum and the iron release by reticuloendothelial cells. Hepcidin expression is upregulated by a variety of stimuli, including inflammation and iron overload, and downregulated by anemia, hypoxia, and iron deficiency. Chronic kidney disease (CKD) is associated with increased serum hepcidin levels, and the increased levels may contribute to the development and severity of anemia and to resistance to erythropoiesis-stimulating agents (ESAs). Elevated serum hepcidin levels contribute to the dysregulation of iron homeostasis in CKD patients. Although parenteral iron supplementation can bypass some of the iron-blocking effects of hepcidin in CKD patients with anemia, and free iron and iron stores increase as a result, the anemia is only partially corrected, and the ESA dose requirements remain significantly higher than needed for physiological replacement. Treatment with agents that lower serum hepcidin levels or inhibit its actions may be an effective strategy for restoring normal iron homeostasis and improving anemia in CKD patients. The aim of this article was to review the regulation of hepcidin levels and the role of hepcidin in CKD-related anemia, and to discuss hepcidin's potential as a clinical biomarker and several investigational treatments designed to lower serum hepcidin levels.
authors: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. tsuchiya@kc.twmu.ac.jp
authors: Ken
authors: K
authors: Tsuchiya
authors: Kosaku
authors: K
authors: Nitta
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000209:etiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron