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

A Correction to this article was published on 05 July 2021

This article has been updated



Recent studies have suggested that erythropoiesis-stimulating agents (ESAs) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis.


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 CD45lowCD34+CD133+ cells.


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.


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.

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This study was supported in part by grants from the Kidney Foundation of Japan (grant number JKFB 17-7 (2017–2019)), and also by research funds from the Japanese Ministry of Health, Labor and Welfare (2015–2017).

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Correspondence to Takashi Naito.

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The study was a conducted in accordance with the Declaration of Helsinki and was approved by the independent Ethics Committee of Tokyo Women’s Medical University (No. 1135) and Tokyo Rosai Hospital (No. 2414).

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Informed consent was obtained from all individuals participants included in the study.

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Naito, T., Shun, M., Nishimura, H. et al. Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients. Clin Exp Nephrol (2021).

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  • Erythropoiesis-stimulating agents
  • Endothelial progenitor cells
  • Recombinant human erythropoietin
  • Darbepoetin
  • Epoetin β pegol