Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to continuous erythropoietin receptor activator administration in hemodialysis patients: a randomized study

Ther Apher Dial. 2014 Oct;18(5):421-6. doi: 10.1111/1744-9987.12161. Epub 2014 Jan 24.

Abstract

Inadequate iron availability limits the response to erythropoiesis-stimulating agents (ESA) and hepcidin is a key regulator of iron metabolism. However, there is little information concerning time-dependent changes in hepcidin in response to the change of accelerated iron demand due to ESA-induced erythropoiesis. In this study, iron-related parameters, including hepcidin levels, were explored in comparison to patients receiving continuous erythropoietin receptor activator (CERA) and epoetin beta (EPO) treatment. Ninety-four patients were randomized to receive monthly CERA (N = 47) or EPO three times/week (N = 47). After the titration period, hemoglobin levels and iron-related parameters were examined. Data for 71 patients were evaluated (CERA, N = 34; EPO, N = 37). Compared with EPO treatment, CERA treatment caused significant decreases within 1 week in hepcidin (-93.5 ± 46.9 vs. -1.3 ± 38.3 ng/mL, P < 0.01), reticulocyte hemoglobin equivalent (Ret-He) (-4.03 ± 2.64 vs. -1.13 ± 1.41 pg, P < 0.01), ferritin (-58.9 ± 30.5 vs. -12.2 ± 23.8 ng/mL, P < 0.01) and transferrin saturation (-13.2 ± 9.1 vs. 1.0 ± 11.9%, P < 0.01) and significant increases within 2 weeks in the levels of hemoglobin (0.42 ± 0.38 vs. -0.02 ± 0.48 g/dL, P < 0.01). In conclusion, hepcidin, Ret-He, ferritin and transferrin saturation levels decreased within 1 week and hemoglobin increased within 2 weeks after CERA administration. Time course of iron-related parameters including hepcidin demonstrated accelerated iron utilization appropriately according to ESA-induced erythropoiesis.

Keywords: Anemia; Epoetin beta pegol; Erythropoiesis stimulating agents; Hemodialysis; Hepcidin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Erythropoiesis / drug effects
  • Erythropoietin / pharmacology*
  • Erythropoietin / therapeutic use
  • Female
  • Ferritins / metabolism
  • Hematinics / pharmacology
  • Hematinics / therapeutic use
  • Hemoglobins / metabolism
  • Hepcidins / metabolism*
  • Humans
  • Iron / metabolism
  • Male
  • Middle Aged
  • Polyethylene Glycols / pharmacology*
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Renal Dialysis*
  • Reticulocytes / metabolism
  • Time Factors
  • Transferrin / metabolism

Substances

  • Hematinics
  • Hemoglobins
  • Hepcidins
  • Recombinant Proteins
  • Transferrin
  • continuous erythropoietin receptor activator
  • epoetin beta
  • Erythropoietin
  • Polyethylene Glycols
  • Ferritins
  • Iron