title: Associations among Erythroferrone and Biomarkers of Erythropoiesis and Iron Metabolism, and Treatment with Long-Term Erythropoiesis-Stimulating Agents in Patients on Hemodialysis.
abstract: BACKGROUND
  We aimed to identify associations between erythroferrone (ERFE), a regulator of hepcidin 25, and biomarkers of erythropoiesis and iron metabolism. We also aimed to determine the effects of erythropoiesis-stimulating agents (ESA), continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) on ERFE production in patients on hemodialysis (HD).
  
  
  METHODS
  Blood samples were obtained from 59 patients before HD sessions on day 0 (baseline). Twenty patients who were injected with either CERA (N = 10) or DA (N = 10) at the end of the dialysis week (day 0), who had ferritin ≥ 100 ng/mL and/or transferrin saturation ≥ 20%, and hemoglobin > 9 g/dL were selected from among the 59 patients. Blood was sampled serially before HD sessions on days 3, 5, 7 from patients on DA and on the same days plus day 14 from those on CERA.
  
  
  RESULTS
  Levels of ERFE correlated inversely with those of hepcidin 25 and ferritin, and positively with those of soluble transferrin receptor. The hepcidin 25: ERFE ratio and hepcidin 25 levels positively correlated with ferritin levels. Levels of ERFE significantly increased from day 3 of treatment with DA and CERA and decreased by days 7 and 14, respectively. Erythropoiesis-stimulating agents concomitantly decreased levels of hepcidin 25 as those of ERFE increased.
  
  
  CONCLUSIONS
  We identified a novel association between ESA and ERFE in patients on HD. Both DA and CERA increased levels of ERFE that regulated hepcidin 25 and led to iron mobilization from body stores during erythropoiesis.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University Koto Toyusu Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Honda
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University, School of Pharmacy, Tokyo, Japan.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University, School of Medicine, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Onuma
authors.affiliation: Shibagaki Dialysis Clinic Jiyugaoka, Tokyo, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Shibagaki
authors.affiliation: Shibagaki Dialysis Clinic Jiyugaoka, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yuza
authors.affiliation: Shibagaki Dialysis Clinic Togoshi, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirao
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University, School of Pharmacy, Tokyo, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Aging Research Unit, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University, School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology / Q000517:prevention & control*; D015415:Biomarkers; D003430:Cross-Sectional Studies; D000068256:Darbepoetin alfa / Q000494:pharmacology* / Q000627:therapeutic use; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000494:pharmacology* / Q000627:therapeutic use; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000096:biosynthesis / Q000502:physiology*; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D011990:Receptors, Transferrin / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects; D017701:Reticulocyte Count; D013997:Time Factors; D014168:Transferrin / Q000032:analysis
chemical_list: D015415:Biomarkers; C000600298:Erfe protein, human; D006397:Hematinics; D006454:Hemoglobins; D064451:Hepcidins; D036361:Peptide Hormones; D011990:Receptors, Transferrin; D014168:Transferrin; C508420:continuous erythropoietin receptor activator; C545475:hepcidin 25, human; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols; D005293:Ferritins; D007501:Iron