肾移植术后巨细胞病毒感染对受者远期肾功能的影响

目的 观察肾移植术后外周血单个核细胞(PBMC)转化生长因子β_1,(TGF-β_1)mRNA表达,探讨巨细胞病毒(CMV)感染对远期肾功能的影响和可能机制.方法 选择2000年3月至2005年12月期间手术受者为研究对象,根据术后CMV感染与发病情况,将完成3年随访的96例受者分成3组:A组为有症状的活动性感染(n=33),B组为无症状的活动感染(n=33),C组为无活动性感染(n=30).分析CMV感染、PBMC内TGF-β_1,mRNA表达和血清肌酐(Scr)三者之间关系,对6例肾功能异常者实施移植肾活检术.结果 术后6月3组Scr水平无明显差异(P>0.05),有症状的A组PBMC的TGF-β_1,mRNA表达水平明显较无症状的B组和C组高(均P<0.01),而术后3年A组Scr水平明显较其它两组高(P<0.01),A组有10例(10/33)出现肾功能异常,发生率较B组(3/33)和C组(3/30)显著增高(均P<0.05).3组肾功能异常者(16例)在术后6月PBMC的TGF-β_1,mRNA表达水平较肾功能正常者(80例)明显增高(P<0.01).肾功能异常患者组织病理提示以间质纤维化、肾小管萎缩改变为主,符合慢性移植肾肾病(CAN)的病理改变.结论 肾移植术后有症状CMV感染是诱发CAN的重要因素,TGF-β_1可能介导了移植肾的损伤,早期监测PBMC内TGF-β_1 mRNA表达对防治CAN发生、发展有一定的临床意义.

Abstract：

Objective To evaluate the effect of cytomegalovirus (CMV) infection following kidney transplantation on long-term renal function and its mechanism. Methods Ninety-six patients undergoing kidney transplantation between March 2000 and December 2005, who completed a 3-year follow-up investigation, were divided into 3 groups according CMV-pp65 antigenemia and clinical symptoms. Group A consisted of 33 recipients with symptomatic active CMV infection, group B included 33 with asymptomatic active CMV infection and group C included 30 with inactive infection. The relation of CMV infection, transforming growth factor-β_1 (TGF-β_1) mRNA in the peripheral blood mononuclear cells (PBMCs) and serum creatinine (Scr) were analyzed, and the grafts in 6 cases with renal dysfunction were biopsied. Results The expression of TGF-(β_1 mRNA in PBMCs was significantly higher in group A than in the other two groups 6 months after the transplantation (P<0.01), while Scr levels showed no significant difference between the 3 groups(P>0.05). Three years later, Scr levels in group A were significantly increased as compared with those in the other two groups (P<0.01), and the rate of renal dysfunction in group A (10/33) was significantly higher than those in group B (3/33) and C(3/30) (P<0.05). In the 16 with renal dysfunction, the expression of TGF-β_1 mRNA in PBMCs significantly higher than that in the other 80 patients with normal renal function (P<0.01). Renal allograft biopsies demonstrated mild or severe interstitial fibrosis, tubular atrophy and mononuclear cell infiltration in the 6 patients with renal graft dysfunction, supporting the diagnosis of chronic allograft nephropathy (CAN). Conclusion Symptomatic active CMV infection in renal allograft recipients is an important factor contributing to the occurrence of CAN. Monitoring of TGF-β_1 mRNA expression in PBMCs proves useful in identifying patients at risk of CAN.     

CRRT在肾移植术后巨细胞病毒性肺炎治疗中的应用

目的探讨连续肾脏替代治疗（CRRT）在治疗肾移植术后巨细胞病毒（CMV）肺炎的疗效。方法2003年1月至2007年12月期间,肾移植术后CMV肺炎30例,分为CRRT组（n=15）和对照组（n=15）,对照组给予常规治疗,CRRT组在常规治疗基础上加用CRRT治疗,采用BM25连续血液净化系统,AN69膜血滤器进行前稀释连续静脉-静脉血液滤过（CVVH）。检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）水平,比较两组呼吸机使用时间、住院时间和病死率。结果发病时（0d）两组血清TNF-α、IL-8水平较发病前显著升高（均P〈0.01）,对照组在治疗7d后TNF-α、IL-8水平继续升高,14d后开始下降,而CRRT组TNF-α、IL-8水平较对照组显著降低（均P〈0.05）。CRRT组呼吸机使用时间（7.2±2.5）d明显较对照组（9.8±3.0）d缩短（P〈0.01）,住院时间（21.2±5.3）d也明显较对照组（26.1±5.5）d缩短（P〈0.01）;CRRT组和对照组分别有3例（3/15）和5例（5/15）患者死亡,病死率比较无统计学差异（P〉0.05）。结论CRRT在治疗肾移植术后CMV肺炎时可有效清除炎症介质,提高救治CMV肺炎的疗效。