Predictors of low circulating endothelial progenitor cell numbers in haemodialysis patients

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2008-08, Vol.23 (8), p.2611-2618
• Main Authors: Schlieper, Georg, Hristov, Mihail, Brandenburg, Vincent, Krüger, Thilo, Westenfeld, Ralf, Mahnken, Andreas H., Yagmur, Eray, Boecker, Georg, Heussen, Nicole, Gladziwa, Ulrich, Ketteler, Markus, Weber, Christian, Floege, Jürgen
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - pathology; Aged; alpha-2-HS-Glycoprotein; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood Cell Count; Blood Proteins - metabolism; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; calcification; Calcinosis - etiology; cardiovascular disease; Case-Control Studies; Cell Adhesion; Cell Movement; Cell Survival; chronic haemodialysis; Coronary Artery Disease - blood; Coronary Artery Disease - etiology; Emergency and intensive care: renal failure. Dialysis management; Endothelial Cells - pathology; endothelial progenitor cells; Female; fetuin-A; Hematocrit; Humans; In Vitro Techniques; Intensive care medicine; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - therapy; Male; Medical sciences; Middle Aged; Renal Dialysis; Reticulocytes - pathology; Risk Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfn103

Background. End-stage renal disease (ESRD) patients exhibit increased cardiovascular mortality associated with cardiovascular calcifications and endothelial dysfunction. As circulating endothelial progenitor cells (EPCs) harbour vascular regenerative potential and are altered in uraemia, we examined clinical and biochemical factors influencing EPC levels as well as the relation between EPC numbers and function and uraemic cardiovascular calcifications. Methods. Sixty-five haemodialysis patients were investigated. Cardiovascular calcifications were assessed by multi-slice spiral CT (MSCT, n = 44) with the calculation of coronary Agatston scores and indirectly by carotid-femoral pulse wave velocity (PWV, n = 61). EPCs were quantified in peripheral blood (CD34+/KDR+) and at day 7 after ex vivo cultivation (ac-LDL+/lectin+) by flow cytometry. In addition, colony-forming units (CFUs), migratory activity, adhesion and viability of isolated EPCs were analysed. Results. EPC numbers were reduced (P < 0.001) compared to 27 healthy controls (−64%) or 81 patients with documented coronary artery disease and normal renal function (−58%). Coronary calcifications did not exhibit a significant association with the numbers of circulating CD34+/KDR+ or isolated ac-LDL+/lectin+ EPCs. No difference in EPC functions was observed between the 10 patients with the lowest Agatston scores (range 0–41) versus those with the highest scores (range 1181–3736). Multivariate analysis revealed low fetuin-A serum levels to be a positive predictor, while haematocrit and reticulocytes were negative predictors of reduced ac-LDL+/lectin+ EPC numbers. Conclusions. EPC numbers and function did not correlate with the degree of coronary calcifications in haemodialysis patients. Rather they appear to be related to serum fetuin-A levels, haematocrit and reticulocytes.