title: HFE mutations and iron in hemodialysis patients.
abstract: In chronic hemodialysis patients, a disruption in iron metabolism ranging from absolute to functional deficiency, with compartmentalization of this metal into macrophages, is often observed. Chronic inflammation indeed often causes an upregulation of the iron hormone hepcidin, thereby reducing iron absorption and availability to the erythron. We systematically reviewed the literature on the role of genetic risk factors on iron metabolism in hemodialysis. In this setting, mutations in the HFE gene of hereditary hemochromatosis may confer an adaptive benefit by decreasing hepcidin release, thus improving iron availability to erythropoiesis, anemia control, and the response to erythropoiesis stimulating agents and iron itself, and reducing the side effects of these therapies. The HFE protein together with Transferrin receptor-2 may also have a direct role on erythroid differentiation and iron uptake in erythroid cells. In addition, other genetic determinants of iron status, such as variants in Matriptase-2 (TMPRSS6), have been shown to influence iron metabolism in chronic hemodialysis patients, most likely acting through hepcidin regulation. Although data must be confirmed in larger prospective studies, this favorable shift in iron metabolism balance possibly results in reduced mortality, in particular because of cardiovascular and infective diseases. Further genetic studies may offer a valuable tool to test these hypotheses and guide personalized clinical management and the research of new therapies.
authors.affiliation: Department of Pathophysiology and Transplantation, Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.affiliation: Department of Pathophysiology and Transplantation, Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pelusi
mesh_terms: D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D006435:Renal Dialysis; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D000071020:Hemochromatosis Protein; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human
keywords: Anemia; HFE; clinical nephrology; inflammation; iron overload