Uremia causes endothelial progenitor cell deficiency

Background. Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular repair. Their number in peripheral blood correlates with endothelial function and cardiovascular risk in humans. We explored whether uremia influences the number of EPCs. Methods. We assessed circulating CD34 + hematopoietic progenitor cells in whole blood using flow cytometry and EPCs (in vitro assay) in 46 patients with advanced renal failure and in 46 age- and gender-matched healthy subjects. Further, the effect of uremia on EPC differentiation was studied in vitro and in vivo. Results. Both in renal patients (r = 0.34, P < 0.02) and in healthy subjects (r = 0.32, P = 0.04) the number of EPCs was significantly correlated to the absolute number of CD34 + hematopoietic progenitor cells. Renal patients had significantly fewer EPCs than healthy subjects, however (167 +/- 15 cells/high power field vs. 235 +/- 17 cells/high power field; P < 0.05). Uremic serum significantly (P < 0.05) inhibited EPC differentiation and functional activity in vitro. Amelioration of uremia after institution of renal replacement therapy in patients with terminal renal failure also significantly (P < 0.05) increased the number of EPCs. Conclusion. Uremia inhibits differentiation of EPCs. This may impair cardiovascular repair mechanisms in patients with renal failure.