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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. [ABSTRACT FROM AUTHOR]

Background. Chronic kidney disease (CKD) is associated with vascular and tissue calcification. The extent of vascular calcification has been identified as an independent risk factor of cardiovascular death in patients on haemodialysis. Methods. We studied the role of fetuin-A in CKD-associated calcification using a mouse model of graded renal insufficiency generated by nephrectomy and high phosphate diet. We used wild-type and fetuin-A-deficient mice on the calcification resistant genetic background C57BL/6 to study the influence on calcification of CKD, dietary phosphate and fetuin deficiency. Hyperphosphataemia, elevated BUN, hyperparathyroidism and von Kossa histochemistry served as indicators of calcification disease. The expression of osteopontin, a marker of osteoblast-like cell differentiation was analyzed by realtime PCR and immunohistechemistry. Results. We detected tissue and genotype-specific susceptibility for calcification. Fetuin-A-deficient mice with CKD and high phosphate diet had only a moderately elevated serum calcium phosphate product (6.9 ± 1.4 mmol2/l2), but suffered severe calcification of kidney, heart and lung. In contrast, wild-type mice under the same conditions developed renal calcinosis only despite an elevated serum calcium phosphate product (9.6 ± 0.9 mmol2/l2). Calcification was preceded by the local induction of osteopontin, a marker for osteoblast-like cell differentiation. Conclusion. Fetuin-A deficiency, CKD and high phosphate diet act synergistically in the pathogenesis of extraosseous calcification. [ABSTRACT FROM AUTHOR]