Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients.

Publisher: Springer Country of Publication: Japan NLM ID: 9709923 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1437-7799 (Electronic) Linking ISSN: 13421751 NLM ISO Abbreviation: Clin Exp Nephrol Subsets: MEDLINE

Publication: 2008- : Tokyo : Springer
Original Publication: Tokyo : Published for the Japanese Society of Nephrology by Churchill Livingstone, c1997-

Anemia/*drug therapy ; Endothelial Progenitor Cells/*drug effects ; Erythropoietin/*pharmacology ; Hematinics/*pharmacology ; Neovascularization, Physiologic/*drug effects; Aged ; Anemia/blood ; Anemia/etiology ; C-Reactive Protein/metabolism ; Cell Count ; Darbepoetin alfa/pharmacology ; Erythropoietin/therapeutic use ; Female ; Ferritins/blood ; Humans ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/therapy ; Male ; Matrix Metalloproteinase 2/blood ; Middle Aged ; Polyethylene Glycols/pharmacology ; Prospective Studies ; Recombinant Proteins/pharmacology ; Renal Dialysis ; Vascular Endothelial Growth Factor A/blood

Background: Recent studies have suggested that erythropoiesis-stimulating agents (ESAs) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis.
Methods: We conducted a 12-week prospective study in 51 dialysis patients; 13 were treated with recombinant human erythropoietin (EPO, 5290.4 ± 586.9 IU/week), 16 with darbepoetin (DA, 42.9 ± 4.3 µg/week), 12 with epoetin β pegol (CERA, 40.5 ± 4.1 µg/week) and 10 with no ESAs. Vascular mediators comprising endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45 ^low CD34 ⁺ CD133 ⁺ cells.
Results: The EPC count increased significantly to a greater extent in the EPO group than in the other three group, and increased significantly from 0 to 12 weeks in a EPO dose-dependent manner. In both the DA and CERA groups, the EPC count did not change at 12 weeks. Serum levels of VEGF, MMP-2 and hs-CRP were not affected by ESA treatment in all groups. In the CERA group, serum ferritin decreased significantly compared to the no-ESA group and correlated with CERA dose, although use of iron was permitted if required during the prospective study period of 12 weeks.
Conclusions: When patients on dialysis were treated with clinical doses of various ESAs, only EPO induced a significant increase of circulating EPCs from bone marrow, whereas, DA and CERA had no effect.
(© 2021. Japanese Society of Nephrology.)

Erratum in: Clin Exp Nephrol. 2021 Sep;25(9):1049-1050. doi: 10.1007/s10157-021-02103-x. (PMID: 34224009)
Erratum in: Clin Exp Nephrol. 2022 Jan;26(1):99. doi: 10.1007/s10157-021-02162-0. (PMID: 34783939)

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JFKB 17-7 Kidney Foundation, Japan

Keywords: Darbepoetin; Endothelial progenitor cells; Epoetin β pegol; Erythropoiesis-stimulating agents; Recombinant human erythropoietin

0 (Hematinics)
0 (Recombinant Proteins)
0 (VEGFA protein, human)
0 (Vascular Endothelial Growth Factor A)
0 (continuous erythropoietin receptor activator)
11096-26-7 (Erythropoietin)
15UQ94PT4P (Darbepoetin alfa)
3WJQ0SDW1A (Polyethylene Glycols)
9007-41-4 (C-Reactive Protein)
9007-73-2 (Ferritins)
EC 3.4.24.24 (MMP2 protein, human)
EC 3.4.24.24 (Matrix Metalloproteinase 2)

Date Created: 20210609 Date Completed: 20220121 Latest Revision: 20220121

20250114

10.1007/s10157-021-02071-2

34106373