de Groot Kirsten, Bahlmann Ferdinand H, Bahlmann Elisabeth, Menne Jan, Haller Hermann, Fliser Danilo
Division of Nephrology, Department of Internal Medicine, Hannover Medical School, 30625 Hannover, Germany.
Transplantation. 2005 Apr 27;79(8):941-5. doi: 10.1097/00007890-200504270-00012.
Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular repair, and their number correlates with endothelial function and cardiovascular risk in humans. In uremic patients, the number of functionally active EPCs is reduced. Thus, we assessed EPCs in stable patients 6 months or more after renal transplantation.
We analyzed circulating CD34+ hematopoietic progenitor cells (HPCs) using flow cytometry and EPCs (in vitro assay) in 74 renal transplant patients (51.6+/-11.5 years; 46 males), 74 age-matched healthy subjects, and 29 patients with preterminal renal failure.
EPC numbers were similar in renal transplant recipients and controls (232+/-92 vs. 250+/-103/high power field; n.s.), but were significantly higher than in uremic patients (160+/-97/high power field; P=0.004). In addition, transplant recipients had more HPCs than controls (2.71+/-1.65 vs. 1.99+/-1.12 /microl; P=0.004) and uremic patients (1.64+/-0.96/microl; P=0.001). EPCs in renal transplant recipients correlated significantly with graft function(that is, Cockcroft-Gault clearance [r=0.294; P=0.012]), but not with age or HPCs. Moreover, in the multiple regression analysis, graft function (r=0.332; P=0.01) and diastolic blood pressure (r=-0.278; P=0.03) were independent predictors of EPCs. In vitro, sera from renal transplant recipients with poor graft function significantly inhibited EPC differentiation compared with sera from patients with a clearance above 50 mL/min (151+/-54 vs. 274+/-94 EPCs/high power field; P=0.02).
EPC numbers in stable renal transplant recipients are comparable to those found in healthy subjects. In addition, graft function is a significant determinant of EPCs. Prospective studies should explore whether improvement of EPCs influences cardiovascular risk in renal transplant recipients.
循环血中的骨髓来源的内皮祖细胞(EPCs)可促进血管修复,其数量与人类的内皮功能及心血管风险相关。在尿毒症患者中,功能活跃的EPCs数量减少。因此,我们评估了肾移植术后6个月或更长时间的稳定患者的EPCs情况。
我们采用流式细胞术分析了74例肾移植患者(年龄51.6±11.5岁;男性46例)、74例年龄匹配的健康受试者以及29例终末期肾衰竭患者循环中的CD34+造血祖细胞(HPCs),并进行了EPCs的体外检测。
肾移植受者和对照组的EPCs数量相似(分别为232±92和250±103/高倍视野;无显著差异),但显著高于尿毒症患者(160±97/高倍视野;P=0.004)。此外,移植受者的HPCs数量多于对照组(分别为2.71±1.65和1.99±1.12/μl;P=0.004)以及尿毒症患者(1.64±0.96/μl;P=0.001)。肾移植受者的EPCs与移植肾功能显著相关(即Cockcroft-Gault肌酐清除率[r=0.294;P=0.012]),但与年龄或HPCs无关。此外,在多元回归分析中,移植肾功能(r=0.332;P=0.01)和舒张压(r=-0.278;P=0.03)是EPCs的独立预测因素。在体外,移植肾功能差的肾移植受者的血清与肌酐清除率高于50 ml/min的患者的血清相比,显著抑制EPCs分化(分别为151±54和274±94 EPCs/高倍视野;P=0.02)。
稳定的肾移植受者的EPCs数量与健康受试者相当。此外,移植肾功能是EPCs的重要决定因素。前瞻性研究应探讨改善EPCs是否会影响肾移植受者的心血管风险。