Effect of moderate-to-severe chronic kidney disease on flow-mediated dilation and progenitor cells

A reduction in progenitor cell populations that help preserve vascular continuity and induce vascularization may accentuate endothelial cell apoptosis and dysfunction, ultimately contributing to organ failure and increased cardiovascular disease in chronic kidney disease (CKD). We hypothesized that CD45+ myeloid and CD34+ hematopoietic circulating progenitor cell (CPC) subpopulations would be reduced, peripheral blood mononuclear cell (PBMNC) colony-forming units (CFU) would be impaired, and flow-mediated dilation (FMD) would be impaired in patients with moderate-to-severe CKD as compared with healthy controls. Eleven moderate-to-severe CKD patients (mean estimated glomerular filtration rate [eGFR]: 36 ± 5) and 14 healthy controls were studied; blood was drawn and FMD was assessed by brachial artery FMD. CPCs were quantified via flow cytometry, and isolated PBMNCs were cultured for the colony-forming assay. CKD patients had significantly impaired FMD; lower CD34+, CD34+/KDR+, CD34+/CD45- and CD34+/KDR+/CD45- hematopoietic CPCs; lower CD45+, CD45+/KDR+, CD34+/CD45+ and CD34+/KDR+/CD45+ myeloid CPCs; and impaired CFUs as compared with healthy controls. Regression analysis revealed that CD34+, CD34+/KDR+ and CD34+/CD45- hematopoietic CPCs were associated positively with eGFR and negatively with blood urea nitrogen and serum creatinine. The CD45+/KDR+ myeloid CPCs also were associated positively with eGFR and negatively with serum creatinine. CD34+ hematopoietic CPCs and CD45+/KDR+ as well as CD34+/CD45+ myeloid CPCs were associated positively with FMD. In conclusion, myeloid and hematopoietic CPCs are reduced and associated with renal function as well as FMD in CKD. Therefore, reductions in CPCs may be a potential mechanism by which vascular integrity is compromised, increasing cardiovascular disease risk and contributing to renal disease progression in CKD.