Submitted on December 18, 2008
Revised on March 26, 2009
Accepted on March 31, 2009
Endothelial Progenitor Cell Dysfunction in Patients with Progressive Chronic Kidney Disease
Guido Krenning1*, Patricia YW Dankers1, Johannes W Drouven1, Femke Waanders, Casper FM Franssen2, Marja JA van Luyn1, Martin C Harmsen1, and Eliane R Popa1
1 University Medical Center Groningen, University of Groningen
2 University Medical Center Groningen
* To whom correspondence should be addressed. E-mail: g.krenning{at}med.umcg.nl.
Endothelial progenitor cells (EPC) contribute to repair and maintenance of the vascular system, but in patients with chronic kidney disease (CKD), the number and function of EPC may be affected by kidney dysfunction. We assessed numbers and angiogenic function of EPC from patients with CKD in relation to disease progression. In a cross-sectional, prospective study, 50 patients with varying degrees of CKD including 20 patients undergoing dialysis and 10 healthy controls were included. Mononuclear cells were isolated and circulating EPC were quantified by flow cytometry based on expression of CD14 and CD34. EPC were cultured on fibronectin-coated supramolecular films of oligocaprolactone under angiogenic conditions to determine their angiogenic capacity and future use in regenerative medicine. CKD patients had normal numbers of circulating CD14+ EPC but reduced numbers of circulating CD34+ EPC. Furthermore, EPC from patients with CKD displayed functional impairments, i.e. hampered adherence, reduced endothelial outgrowth potential and reduced antithrombogenic function. These impairments were already observed at Stage 1 of CKD and became more apparent when CKD progressed. Dialysis treatment only partially ameliorated EPC impairments in patients with CKD. In conclusion, EPC number and function decrease with advancing CKD which may hamper physiological vascular repair and can add to the increased risk for cardiovascular diseases observed in CKD patients.
