Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina

• Published in: Nephrology, dialysis, transplantation Vol. 23; no. 7; pp. 2265 - 2273
• Main Authors: Surdacki, Andrzej, Marewicz, Ewa, Wieteska, Ewa, Szastak, Grzegorz, Rakowski, Tomasz, Wieczorek-Surdacka, Ewa, Dudek, Dariusz, Pryjma, Juliusz, Dubiel, Jacek S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2008; Oxford Publishing Limited (England)
• Subjects: Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angina Pectoris - immunology; Angina Pectoris - pathology; Antigens, CD34 - metabolism; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Cell Count; coronary artery disease; Coronary Artery Disease - epidemiology; Emergency and intensive care: renal failure. Dialysis management; endothelial progenitor cells; Endothelium, Vascular - physiopathology; Glomerular Filtration Rate - physiology; Humans; Intensive care medicine; Male; Medical sciences; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - pathology; Middle Aged; Multivariate Analysis; renal insufficiency; Renal Insufficiency - immunology; Renal Insufficiency - pathology; Renal Insufficiency - physiopathology; Risk Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vascular Endothelial Growth Factor Receptor-2 - metabolism; coronary artery disease; endothelial progenitor cells; renal insufficiency; Kidney disease; Endothelial cell; Urinary system disease; Hemodialysis; Cardiovascular disease; Angina pectoris; Coronary heart disease; Extrarenal dialysis; Depletion; Renal failure; Progenitor cell
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfm943

Background. Low blood counts of CD34/kinase-insert domain receptor double-positive cells (CD34+/KDR+ cells)—a leukocytes subpopulation enriched for bone marrow-derived endothelial progenitor cells (EPC)— predict adverse outcomes in coronary artery disease (CAD). The dependence of EPC numbers on the glomerular filtration rate (GFR), another prognostic factor, has not been reported in CAD yet. Our aim was to assess CD34+/KDR+ cell counts versus GFR in stable angina. Methods. We studied 102 stable angina men with severe angiographic CAD and normal left-ventricular systolic function. CD34+/KDR+ cells were enumerated by flow cytometry. Results. With lowering GFR, CD34+/KDR+ cell numbers (% of lymphocytes, median and interquartile range) decreased: 0.04 (0.03–0.06), 0.03 (0.02–0.05) and 0.02 (0.01–0.03)% for GFR ≥90, 60–89 and 30–59 ml/min/1.73 m2, respectively (P < 0.001 for trend). CD34+/KDR+ cell counts correlated with GFR (r = 0.25, P = 0.01), CAD extension score (r = −0.20, P = 0.04), soluble form of vascular cell adhesion molecule-1 (sVCAM-1) (r = −0.22, P = 0.03) and homocysteine (r = −0.20, P = 0.04) levels. A GFR <90 ml/min/1.73 m2 was associated with insignificantly higher plasma erythropoietin concentrations (r = −0.22, P = 0.09 for trend) that correlated with haemoglobin levels (r = −0.33, P = 0.01, n = 59). The GFR–CD34+/KDR+ cells relation was attenuated, yet maintained (β = 0.19 ± 0.09, P = 0.04) on adjustment for the remaining multivariate determinants of CD34+/KDR+ cell numbers: sVCAM-1 (β = −0.20 ± 0.09, P = 0.03) and haemoglobin (β = 0.18 ± 0.09, P = 0.05). Conclusions. Mild-to-moderate renal dysfunction accompanying stable angina is associated with CD34+/KDR+ cell depletion, which partially depends on concomitant endothelial dysfunction and a tendency to anaemia (despite insignificantly higher erythropoietin) irrespective of an angiographic CAD extent. This may exacerbate an imbalance between endothelial injury and EPC-mediated repair, thus contributing to high cardiovascular risk in CAD coexisting with renal insufficiency.