Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to continuous erythropoietin receptor activator administration in hemodialysis patients: a randomized study.
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.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Midori
M
Kakimoto-Shino
Yoshiyuki
Y
Toya
Tadashi
T
Kuji
Tetsuya
T
Fujikawa
Satoshi
S
Umemura
D000368:Aged; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D006435:Renal Dialysis; D012156:Reticulocytes / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
D006397:Hematinics; D006454:Hemoglobins; D064451:Hepcidins; D011994:Recombinant Proteins; D014168:Transferrin; C508420:continuous erythropoietin receptor activator; C103998:epoetin beta; D004921:Erythropoietin; D011092:Polyethylene Glycols; D005293:Ferritins; D007501:Iron
Anemia; Epoetin beta pegol; Erythropoiesis stimulating agents; Hemodialysis; Hepcidin