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
Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
Nephrol Dial Transplant. 2008 Aug;23(8):2611-8. doi: 10.1093/ndt/gfn103. Epub 2008 Mar 19.
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.
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.
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.
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.
终末期肾病（ESRD）患者心血管死亡率增加，与心血管钙化和内皮功能障碍相关。由于循环内皮祖细胞（EPCs）具有血管再生潜力且在尿毒症中发生改变，我们研究了影响EPC水平的临床和生化因素，以及EPC数量和功能与尿毒症心血管钙化之间的关系。
对65例血液透析患者进行了研究。通过多层螺旋CT（MSCT，n = 44）评估心血管钙化情况，计算冠状动脉阿加西评分，并通过颈股脉搏波速度（PWV，n = 61）进行间接评估。通过流式细胞术对外周血（CD34(+)/KDR(+)）和体外培养7天后（ac-LDL(+)/凝集素(+)）的EPC进行定量分析。此外，还分析了分离的EPC的集落形成单位（CFUs）、迁移活性、粘附性和活力。
与27名健康对照者（降低64%）或81名有冠状动脉疾病记录且肾功能正常的患者（降低58%）相比，EPC数量减少（P < 0.001）。冠状动脉钙化与循环CD34(+)/KDR(+)或分离的ac-LDL(+)/凝集素(+) EPC数量之间未显示出显著相关性。阿加西评分最低（范围0 - 41）的10例患者与评分最高（范围1181 - 3736）的患者之间，EPC功能未观察到差异。多变量分析显示，低胎球蛋白-A血清水平是ac-LDL(+)/凝集素(+) EPC数量减少的阳性预测指标，而血细胞比容和网织红细胞是阴性预测指标。
血液透析患者的EPC数量和功能与冠状动脉钙化程度无关。相反，它们似乎与血清胎球蛋白-A水平、血细胞比容和网织红细胞有关。
