Target Of Rapamycin Inhibitors (Sirolimus And Everolimus) Protocol Versus Cyclosporine Protocol For Initial Immunosuppression Of Kidney Transplatation Recipients: A Meta-analysis Of Randomized Trials

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.