【作者】 胡小红；

【导师】 陈江华；

【作者基本信息】 浙江大学 ， 临床医学， 2009， 硕士

【摘要】 [目的]应用Meta分析方法对肾移植术后免疫抑制治疗雷帕霉素靶蛋白抑制剂方案和环孢霉素方案的疗效和不良反应进行评价。[方法]检索PubMed、EMBASE、Cochrane library等数据库,全面收集有关文献。制定文献纳入标准,符合纳入标准的文献按Jadad评分进行文献质量评估。应用ReviewManager5.0软件进行Meta分析,计算雷帕霉素靶蛋白抑制剂方案组和环孢霉素方案组的患者生存率、移植肾存活率、移植肾急性排斥、肾功能(包括血清肌酐水平、内生肌酐清除率、GFR)、24小时蛋白尿、血压、平均降压药种类、不良反应(包括骨髓抑制作用、脂质代谢紊乱、肺炎、肿瘤、齿龈增生、震颤、腹泻等)的相对危险度(RR)或加权均数差值(WMD)及其95%CI。[结果]共检索到符合纳入标准的相关文献14篇,均为英文文献,其中雷帕霉素靶蛋白抑制剂方案组860例,环孢霉素方案组792例,共1652例。Meta分析结果显示雷帕霉素靶蛋白抑制剂方案组较环孢霉素方案组有更好的肾功能:GFR和Ccr水平较较环孢霉素方案组高10.29 ml/min和10.17 ml/min(分别为:6个随机对照试验,1076例;WMD,10.29 ml/min;95%CI,8.31～12.27,P＜0.00001;4个随机对照试验,252例;WMD,10.17 ml/min;95%CI,6.81～13.53,P＜0.00001),而血肌酐水平较环孢霉素方案组低0.36 mg/dl(8个随机对照试验,374例;WMD,-0.36 mg/dl;95%CI,-0.45～-0.27,P＜0.00001)。与环孢霉素方案组相比,雷帕霉素靶蛋白抑制剂方案组有较高的急性排斥率(7个随机对照试验,1228例;RR,1.35;95%CI,1.13～1.62,P=0.0009),但患者生存率和移植肾存活率无明显差异,分别为8个随机对照试验,1311例;RR,0.98;95%CI,0.96～1.01,P=0.13;和10个随机对照试验,1490例;RR,1.02;95%CI,0.98～1.05,P=0.37。但是对随访时间不短于2年的研究对象进一步进行亚组分析发现,雷帕霉素靶蛋白抑制剂方案组移植肾存活率较高(4个随机对照试验,362例;RR,1.10;95%CI,1.02～1.18,P=0.02)。此外,两组相比,雷帕霉素靶蛋白抑制剂方案组的震颤和齿龈增生的发生率较低,血压更易控制;24小时尿蛋白量、肿瘤发生率和新增的高血糖发生率无明显差异;但骨髓抑制、脂质代谢紊乱、腹泻和肺炎的发生率却高于环孢霉素方案组。[结论]本研究分析发现,总体上来讲,雷帕霉素靶蛋白抑制剂方案和环孢霉素方案的患者生存率和移植肾存活率等终点指标无明显统计学差异,一些关于移植肾的观察指标倾向于雷帕霉素靶蛋白抑制剂方案更有利,比如肾功能相对较好,大于2年的移植肾存活率相对较高,而另一些关于患者的指标如骨髓抑制作用、脂质代谢异常、肺炎等的风险却在雷帕霉素靶蛋白抑制剂方案中更高。确切的疗效和不良作用的观察仍有待于大规模、多中心随机对照临床研究长期随访来证实。更多还原

【Abstract】 ObjectiveThis study aimed to assess outcomes of TOR-I protocol versus ciclosporin(CsA) protocol for initial immunosuppression of kidney transplatation recipients with meta-analytical techniques.MethodsA literature search was performed for studies comparing kidney transplants from TOR-I protocol versus ciclosporin protocol for initial immunosuppression of kidney transplatation recipients between 1966 and 2008.The following outcomes were evaluated:patient survival,graft survival,acute rejection,graft function(creatinine or GFR or Ccr),daily proteinuria,BP(SBP.DBP,MAP),mean number of antihypertention drugs,adverse events(bone marrow suppression and lipid disturbance,infection, malignancy,gingival hyperplasia,tremor,diarrhoea).ResultsFourteen comparative studies of 1652 patients matched the inclusion criteria,860 for TOR-I protocol and 792 for ciclosporin protocol.Patients treated with TOR-I protocol had better kidney function,showed a significantly higher GFR levels(six trials, 1076 patients;WMD,10.29 ml/min;95%CI,8.31 to 12.27),Ccr levels(four trials, 252patients;WMD,10.17 ml/min;95%CI,6.81 to 13.53),and lower serum creatinine (eight trials,374 patients;WMD,-0.36 mg/dl;95%CI,-0.45 to -0.27).Though there was higher acute rejection(seven trials,1228 patients;RR,1.35;95%CI,1.13 to 1.62, P=0.0009;heterogeneity chi-square=3.87,P=0.69) in TOR-I protocol group,no difference in patient survival(eight trials,1311 patients;RR,0.98;95%CI,0.96 to 1.01),graft survival(ten trials,1490 patients;RR,1.02;95%CI,0.98 to 1.05) and proteinuria(WMD 0.04 g/d;95%CI,-0.23 to 0.30)was observed irrespective of the follow-up time.However,subgroup analysis showed that graft survival was longer(four trials,362patients;RR,1.10;95%CI,1.02 to 1.18)in TOR-I protocol recipients whose follow-up duration was not less than 2 years.For TOR-I protocol in the comparison,there were less tremor,gingival hyperplasia,no significant difference in malignancy and hyperglycaenia,but more bone marrow suppressed,lipid disturbance, diarrhoea and pneumonia risk.Additionally,compared with CsA,TOR-I patients showed a tendency of lower blood pressure and were easier to be controlled.ConclusionGenerally,some surrogate endpoints for graft survival favor TOR-I protocol(higher kidney function,better long-term graft survival though higher risk of acute rejection ),and some for patient outcomes are worsened by TOR-I(bone marrow suppression,lipid disturbance,diarrhoea and pneumonia risk).Long-term hard-endpoint data from methodologically robust randomized trials are still required.更多还原