Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D
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Aims: Circulating endothelial progenitor cells (EPCs) play a pivotal role in vasculogenesis and promote angiogenesis by secreting growth factors. Recent studies have suggested that erythropoietin (EPO) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. The aim of this study was to investigate whether two erythropoiesis-stimulating agents (ESAs) modulate vascular-related factors and EPC mobilization in patients with chronic kidney disease stage G5 and dialysis (CKD G5 and 5D). Materials and methods: We conducted a 12-week prospective study in 63 patients; 21 patients received recombinant human erythropoietin (rhEPO) (EPO group, 4,565.5 +/- 1,994.4 IU/week), 21 patients received darbepoetin (DA) (DA group, 40.1 +/- 13.8 mu g/week), and 21 patients received no ESAs (no-ESA group). Vascular mediators, including EPCs, vascular endothelial growth factor, matrix metalloproteinase- 2 (MMP-2), high-sensitivity C-reactive protein, and asymmetric dimethyl arginine, were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45(low)CD34(+) CD133(+) cells. We also performed a subanalysis of dialysis (5D) patients (n = 32) in the three groups. Results: In the EPO group, EPC count increased significantly from 0 to 12 weeks in a dose-dependent manner (r = 0.62, p = 0.005), and the increase was more conspicuous in the subgroup of dialysis 5D patients. In the DA group, the EPC number did not change at 12 weeks. Neither rhEPO nor DA affected the serum levels of the aforementioned biomarkers other than EPC. Conclusion: We speculate that the pleiotropic effects of rhEPO and DA beyond their hematopoietic effects may differ between CKD G5 and 5D patients.