title: Hepcidin: clinical utility as a diagnostic tool and therapeutic target.
abstract: Iron is essential for life, yet excessive iron can damage tissues and organs. To prevent iron deficiency and overload, iron balance is regulated by the hormone hepcidin. Hepcidin levels increase in response to iron sufficiency, decreasing intestinal iron absorption and inhibiting release of iron from stores and macrophages. Iron deficiency lowers hepcidin, leading to enhanced iron absorption and mobilization of iron from stores. Hepcidin is also increased by inflammation, and has a major role in the anemia of chronic disease. Chronic kidney disease (CKD) is associated with increased hepcidin levels, and this likely contributes to the incidence and severity of anemia, and resistance to erythropoiesis-stimulating agents (ESAs). Elevated hepcidin contributes to the dysregulation of iron homeostasis in CKD. In patients with CKD, although parenteral iron in CKD can bypass some of the iron-blocking effects of hepcidin, free iron and iron stores increase, anemia is only partially corrected, and ESA dose requirements remain significantly higher than physiological replacement. Agents that lower hepcidin or inhibit its actions may be effective strategies to restore normal iron homeostasis, and overcome anemia of chronic kidney disease. We review the regulation of hepcidin, its role in CKD-related anemia, and discuss the potential for hepcidin as a clinical marker, and several investigational methods to lower hepcidin for treatment of anemia in CKD.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA. DCoyne@wustl.edu
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Coyne
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D006397:Hematinics / Q000627:therapeutic use; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011487:Protein Conformation; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D006397:Hematinics; D064451:Hepcidins; D007501:Iron