维持性血液透析患者巨细胞病毒感染与T细胞衰老及心血管疾病的相关性  

Association of cytomegalovirus infection with T cell senescence and cardiovascular diseases in maintenance hemodialysis patients

作　　者：项方方 曹学森 陈晓泓 张臻 沈波 邹建洲 滕杰 丁小强[1,2,3,4,5,6] Xiang Fangfang;Cao Xuesen;Chen Xiaohong;Zhang Zhen;Shen Bo;Zou Jianzhou;Teng Jie;Ding Xiaoqiang(Department of Nephrology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Institute of Kidney and Dialysis,Shanghai 200032,China;Shanghai Medical Center of Kidney,Shanghai 200032,China;Shanghai Key Laboratory of Kidney and Blood Purification,Shanghai 200032,China;Hemodialysis Quality Control Center of Shanghai,Shanghai 200032,China;Department of Nephrology,Zhongshan Hospital(Xiamen),Fudan University,Xiamen 361006,China;Nephrology Clinical Quality Control Center of Xiamen,Xiamen 361006,China)

机构地区：[1]复旦大学附属中山医院肾内科,上海200032 [2]上海市肾病与透析研究所,上海200032 [3]上海市肾脏疾病临床医学中心,上海200032 [4]上海市肾脏疾病与血液净化重点实验室,上海200032 [5]上海市血液透析质量控制中心,上海200032 [6]复旦大学附属中山医院厦门分院肾脏科,厦门361006 [7]厦门市肾病专业质量控制中心,厦门361006

出　　处：《中华肾脏病杂志》2023年第9期656-662,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金(82000705);上海市申康医院发展中心“上海市肾脏内科联盟”项目(SHDC2202230);上海市“科技创新行动计划”长三角科技创新共同体领域项目(21002411500)。

摘　　要：目的探讨维持性血液透析(maintenance hemodialysis,MHD)患者巨细胞病毒(cytomegalovirus,CMV)感染情况及其与T细胞衰老和心血管疾病(cardiovascular disease,CVD)的关系。方法该研究为单中心横断面观察性研究。收集2021年1月至2021年4月于复旦大学附属中山医院血液净化中心接受MHD大于6个月、年龄大于18岁的患者,收集患者临床及血清学资料,采用罗氏Elecsys方法检测CMV抗体水平,流式细胞术检测外周血T细胞CD28表达情况。组间抗CMV IgG水平比较采用Mann-WhitneyU检验或Kruskal-WallisH检验。抗CMV IgG与CD28-T细胞关系采用Spearman相关性分析和多因素线性回归分析。抗CMV IgG与CVD的关系采用Logistic回归分析。结果共纳入438例MHD患者,其中男性270例(61.6%),女性168例(38.4%),中位年龄62(51,70)岁,中位透析龄57(21,100)个月。患者原发病包括慢性肾小球肾炎[213例(48.6%)]、糖尿病肾病[82例(18.7%)]、多囊肾[34例(7.8%)]、高血压肾损害[34例(7.8%)]等。438例MHD患者中,430例(98.2%)患者抗CMV IgG阳性,206例(47.0%)患者抗CMV IgG>500 U/ml。年龄超过70岁者CMV感染率为100%,透析时间>5年者CMV感染率较高(99.1%),但与其他透析时间组差异无统计学意义。Spearman相关分析结果显示,MHD患者抗CMV IgG水平与CD4+CD28-T细胞比例、CD8+CD28-T细胞比例均呈正相关(r=0.316,P<0.001;r=0.272,P<0.001)。多因素线性回归分析结果显示,校正年龄、性别后,lg[CD4+CD28-T细胞(%)]增加、lg[CD8+CD28-T细胞(%)]增加分别与lg[抗CMV IgG水平(U/ml)]升高相关(β=0.455,t=8.315,P<0.001;β=0.412,t=7.282,P<0.001)。根据年龄和抗CMV IgG中位数将患者分为6组,组1:年龄≤55岁,抗CMV IgG<400 U/ml;组2:年龄≤55岁,抗CMV IgG≥400 U/ml;组3:55岁<年龄≤65岁,抗CMV IgG<400 U/ml;组4:55岁<年龄≤65岁,抗CMV IgG≥400 U/ml;组5:年龄>65岁,抗CMV IgG<400 U/ml;组6:年龄>65岁,抗CMV IgG≥400 U/ml。各组间CVD发病率差异有统计学意义(χ^(2)=18.780,P=0.002);相�Objective To evaluate the influence of cytomegalovirus(CMV)infection on T cell senescence and cardiovascular disease(CVD)in maintenance hemodialysis(MHD)patients.Methods It was a single center cross sectional study.Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled.Demographic,hematological,nutritional and inflammatory markers were obtained.Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay.CD28-T cell was evaluated by flow cytometry.Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups.Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28-T cell compartment.Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD.Results A total of 438 MHD patients(270 men and 168 women)were enrolled in the study.The median age was 62(51,70)years.The median time on hemodialysis was 57(21,100)months.The primary diseases included chronic glomerulonephritis[213 cases(48.6%)],diabetic nephropathy[82 cases(18.7%)],polycystic kidney disease[34 cases(7.8%)],hypertensive renal disease[34 cases(7.8%)],etc.Of these patients,430(98.2%)were seropositive for anti-CMV-IgG,206(47.0%)had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml.Patients aged over 70 years old were 100%seropositive for anti-CMV-IgG.Patients on HD for more than 5 years had a higher seropositive rate of 99.1%than those with shorter HD duration,although these results were not statistically significant.Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4+CD28-T cells and CD8+CD28-T cells(r=0.316,P<0.001;r=0.272,P<0.001).Multiple linear regression analysis showed that after adjusting for age and gender,lg[CD4+CD28-T cells(%)]and lg[CD8+CD28-T cells(

关 键 词：肾透析 心血管疾病 巨细胞病毒感染 T淋巴细胞 细胞衰老 

分 类 号：R692.5[医药卫生—泌尿科学] R54[医药卫生—外科学]