title: Greater potency of darbepoetin-α than erythropoietin in suppression of serum hepcidin-25 and utilization of iron for erythropoiesis in hemodialysis patients.
abstract: BACKGROUND
  The potency of darbepoetin-α (DPO-α) to improve anemia in hemodialysis (HD) patients is greater than that of recombinant human erythropoietin (rHuEPO).
  
  
  METHODS
  To assess the potency of DPO-α to mobilize iron from body stores in comparison with rHuEPO in HD patients without apparent inflammation or infection, serum iron, transferrin saturation (TSAT), ferritin, and hepcidin-25 were measured serially. This study included (i) a long-term crossover study for 3 yr to compare the effects of the two erythropoiesis-stimulating agents (ESA) on serum iron, TSAT, and ferritin, and (ii) a short-term crossover study for 8 wk to examine their effects on serum hepcidin-25 in HD patients.
  
  
  RESULTS
  The long-term crossover study demonstrated that the change of ESA from rHuEPO to DPO-α significantly decreased serum ferritin while serum iron and TSAT remained unchanged, while DPO-α as well as rHuEPO maintained hemoglobin level in the target range between 10.0 and 11.0 g/dL. Furthermore, in the short-term crossover study, area under the percent suppression of serum hepcidin-25 time curve for the first 7 d during the DPO-α treatment period was significantly greater than that during the rHuEPO period (348.0 ± 92.4 vs. 178.4 ± 131.5%.day P = 0.030). The greater suppression of hepcidin-25 by DPO-α may facilitate iron mobilization, resulting in diminution of body iron stores without any significant effect on serum iron utilizable for erythropoiesis.
  
  
  CONCLUSIONS
  This study demonstrated that DPO-α has a greater advantage than rHuEPO in that it facilitates iron mobilization from body stores into bone marrow to induce effective erythropoiesis and thus could protect against possible harmful effects caused by excessive iron stores in the body.
authors.affiliation: Shirasagi Hospital, Osaka, Japan.
authors.forename: Shigeichi
authors.initials: S
authors.lastname: Shoji
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.forename: Senji
authors.initials: S
authors.lastname: Okuno
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ichii
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurihara
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors* / Q000097:blood; D019540:Area Under Curve; D018592:Cross-Over Studies; D000068256:Darbepoetin alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D006397:Hematinics; D006454:Hemoglobins; D064451:Hepcidins; D011994:Recombinant Proteins; C545475:hepcidin 25, human; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D005293:Ferritins; D007501:Iron