内皮祖细胞与维持性血液透析患者心血管并发症的关系

Relationship between endothelial progenitor cells and cardiovascular diseases in maintenance hemodialysis patients

目的观察循环内皮祖细胞（EPC）数量变化与维持性血液透析（MHD）患者心血管并发症的关系，探讨EPC在MHD患者心血管并发症发生发展中的作用。方法选取上海交通大学医学院附属仁济医院血液透析中心透析龄超过6个月且年龄在18周岁以上的稳定血液透析患者115例。根据患者的病史、心电图（EKG）、心脏超声、外周血管造影和心血管造影结果，将患者分为心血管疾病（CVD）组和非CVD组。分别留取患者的外周血5ml，采用流式细胞术检测单个核细胞中CD34、CD133、血管内皮细胞生长因子受体2（VEGFR2）三阳性细胞的数量，作为循环内皮祖细胞的数量，比较CVD和非CVD患者的循环EPC数量。运用Logistic回归方法分析MHD患者循环EPC的减少与并发CVD风险的关系。115例MHD患者共随访3年，比较两组新发CVD事件及死亡情况，探讨EPC数量与新发CVD事件及死亡的关系。结果115例患者平均年龄（61．57±12．76）岁，男女比例71：44，平均透析龄（86．24±56.31）个月，平均Kt／V 1．69±0．29，平均超滤量（2．48±0．90）L。115例患者中并发CVD患者44例（38．3％）。CVD患者的循环EPC数量较非CVD患者显著减少（P=0．015），血磷水平更高（P=0．013），糖化血红蛋白水平更高（P〈0．001），而血钙和全段甲状旁腺素（iPTH）等其他生化指标两组间差异无统计学意义。多因素Logistic回归分析显示，增龄（OR=1．061）、糖尿病史（OR=9．796）、透析龄增加（OR=1．015）、血磷水平升高（OR=3．766）、循环EPC数量减少（OR=0.909）是MHD患者发生CVD的独立危险因素。2012年12月至2015年12月共随访3年，115例MHD患者中新发CVD事件22例，其中CVD组9例，非CVD组13例，两组比较差异无统计学意义（P=0．776）；死亡病例共16例，其中CVD组9例，非CVD组7例，两组比较差异无统计学意义（P=0．111）。71例非CVD组患者按EPC中位数分成两组，其中高EPC数量组发生CVD事件3例，低EPC数量组发生CVD事件10例，差异有统计学意义（P=0．024）。结论MHD患者循环EPC数量减少可能与CVD的发生有关；即使经年龄、性别、糖尿病、透析龄、血磷水平校正，循环EPC数量减少仍然是MHD患者CVD发生的独立危险因素。MHD患者循环EPC数量减少可能用来预测心血管事件的发生。

Objective To investigate the relationship between the variation of endothelial progenitor cells （EPC） number and cardiovascular diseases （CVD） in maintenance hemodialysis （MHD） patients, and discuss the function of EPC in the progression of CVD in MHD. Methods One hundred and fifteen MHD patients over 18 years whose dialysis vintage was over six months from Department of Nepbrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. They were divided into CVD group and non- CVD group by medical history, electrokardiographie （EKG）, cardiac ultrasound, peripheral vascular imaging and cardiovascular imaging. Peripheral blood （5 ml） was collected for detecting EPC number by flow cytometry as CD34/ CD133/vascular endothelial growth factor receptor 2 （VEGFR2） cells. The EPC number between CVD group and non-CVD group was compared. The relationship between the decrease of EPC number and CVD risks in MHD patients was analyzed by logistic regression analysis. In a three-year follow-up, the death and new CVD events of the two groups were compared in order to discuss the relationship between EPC number and adverse events. Results Among 115 MHD patients, the average age was 61.57±12.76, male/female was 71/44, the average dialysis vintage was （86.24±56.31） months, the average Kt/V was 1.69±0.29 and average uhrafiltration volume was （2.48±0.90） L. Forty-four patients in 115 （38.3%） were with concurrent CVD. The EPC number in CVD group was significantly lower than that in non CVD group （P=0.015）. The CVD group had higher serum phosphate （P=O.O13）, higher glycosylated hemoglobin （P 〈 0.001）, but serum calcium, intact parathyroid hormone （iPTH） and other indicators had no significant difference between two groups. Multiple Logistic regression analysis showed that older age （OR=1.061）, history of diabetes （OR=9.796）, dialysis vintage （OR=1.015）, serum phosphate （OR=3.766）, decrease of EPC number （OR=0.909） were the independent impact factors of CVD events in MHD patients. There were 22 patients of the 115 MHD patients had encountered a new CVD event in a three-year follow-up between December 2012 and December 2015, 9 patients from the CVD group and 13 patients from the Non-CVD group, and there was no significant difference between two groups （P=0.776）. Nine patients from the CVD group and 7 patients from the Non-CVD group died in the follow-up, and there was no significant difference （P=0.111）. Seventy-one MHD patients from the non-CVD group were divided into two groups by the median of EPC number. There were 3 patients in the higher EPC number group encountered CVD events and 10 patients in the lower EPC number group encountered CVD events, which had significant difference （P=0.024）. Conclusion The decrease of circulating EPC number may be related with CVD events in MHD patients. Even adjusted by age, sex, diabetes, dialysis vintage and serum phosphate, decreased EPC number is still the independent risk factor of CVD events in MHD patients. The decrease of EPC number in MHD patients may be used to predict the occurrence of cardiovascular events.