
Associations among Darbepoetin-α, CD34+ Cells and Cardiovascular Disease Events in Patients on Hemodialysis
Author(s) -
Daisuke Sanada,
Hirokazu Honda,
Noriyuki Kato,
Akio Yokochi,
Tetsuo Michihata,
Tadao Akizawa
Publication year - 2012
Publication title -
nephron extra
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.413
H-Index - 7
ISSN - 1664-5529
DOI - 10.1159/000341855
Subject(s) - medicine , cd34 , erythropoiesis , endocrinology , stem cell , anemia , biology , genetics
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-β (n = 22), darbepoetin-α (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-α and control groups, respectively. CD34+ cells were counted after 6 and 12 months of darbepoetin-α 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-α dose. A low, but not a high, dose of darbepoetin-α for 6 and 12 months was associated with more CD34+ cells. Although high-dose darbepoetin-α 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