Associations Among Darbepoetin-Alpha, Cd34(+) Cells And Cardiovascular Disease Events In Patients On Hemodialysis

Background and Objectives: Erythropoiesis-stimulating agents (ESAs) might moderate circulating CD34-positive hematopoietic stem (CD34(+)) cells. We assessed associations between ESA therapy and CD34(+) cells and their impact on cardiovascular disease (CVD) events in patients on prevalent hemodialysis (HD). Design, Setting, Participants and Measurements: We analyzed 95 patients on prevalent HD who received the ESAs epoetin-alpha (n = 22), darbepoetin-alpha (n = 60), or neither (control; no ESA, n = 13). Baseline values for CD34+ cells, high-sensitivity C-reactive protein, interleukin-6, vascular endothelial growth factor, inter-cellular adhesion molecule-1, and carotid intima-media thickness were determined. The numbers of CD34(+) /erythropoietin receptor (EPOR)+ cells were determined in 35 and 8 patients in the darbepoetin-alpha and control groups, respectively. CD34+ cells were counted after 6 and 12 months of darbepoetin-alpha treatment (n = 35). All patients were followed up for a mean of 28 months. Results: Hemoglobin levels were lower, carotid intima-media thickness was more pronounced, and the ESA dose was higher in patients with a low, than with a high, CD34(+) cell count. The ratio of CD34(+) /EPOR+ to CD34+ cells positively correlated with the darbepoetin-alpha dose. A low, but not a high, dose of darbepoetin-alpha for 6 and 12 months was associated with more CD34+ cells. Although high-dose darbepoetin-alpha therapy was an independent predictor of composite CVD events, this association disappeared when adjusted for the CD34(+) cell count with other confounders. Conclusions: High-dose ESA therapy is associated with a low CD34(+) cell count and comprises a risk factor for CVD events in patients on prevalent HD. Copyright (C) 2012 S. Karger AG, Basel