| Cyclosporine A was used in organ transplantation since 1980'. From then up to now, organ transplantation was into "Cyclosporine era ". Cyclosporine A has to be the most extensive immunodepressant. In recent years new immunodepressant emerging prominently, choosing for difference scheme or formulations of cyclosporine A were became the puzzle of organ transplantation. There is need to provide evidence to solve those problem by systematic review.Renal transplantation is the most common entity organ transplantation in the world , in which, cyclosporine A is the most common using immunodepressant. In order to provide dependable evidence for selection schedule and immunodepressant , we used Cochrane systematic review to evaluate the efficacy and safety of cyclosporine A after renal transplantation.The Systematic Review include three parts: Part â… : Systematic review for efficacy and safety of microemulsion and conventional formulations for cyclosporine A after renal transplantation. Part â…¡: Systematic review for long-term efficacy and safety for normal dose versus withdrawal of cyclosporine A after renal transplantation. Partâ…¢: Systematic Review for comparison tacrolimus and cyclosporine A after renal transplantation.Part â… :Systematic review for efficacy and safety of microemulsion and conventional formulations for cyclosporine A after renal transplantation.Objective:To evaluate the efficacy and safety for conventional formulations and microemulsion cyclosporine A on transplanted renal function, blood pressure, the survival rate of grafts or patients after renal transplantation.Methods:We searched MEDLINE (1989 through Nov.2004.); EMBASE (1989 through Nov.2004.)); The Chinese Biomedical Database (CBM) (1998 through Nov.2004.); Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4;2004) and handsearched 8 Chinese journals and correlative websites, such as 'google'. The studies covered the references of eligible studies were additionally searched. Comparing tacrolimus with cyclosporine A after renal transplantation were included. At least two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the the eligible studies, with confirmation of cross-check. Different opinions would be decided by the third party. The quality of included studies such as randomization, blinding, allocation concealment was evaluated. Meta -analysis was performed using RevMan 4.2.7 software. After heterogeneity test, data without heterogeneity could be pooled using fixed effect model, and those with heterogeneity could be solvedby sensitivity analysis, subgroup analysis or randomized effect model. We will compare outcome measures for binary data using relative risks (RR) with 95% confidence intervals (CI). For continuous data, we will use the weighted mean difference (WMD). We will report medians and ranges in tables only.Results: Nine studies involving 2,290 patients were included. According to the results of meta-analysis, there was no significant difference on the rate of delayed primary function within 6 months between conventional formulations and microemulsion cyclosporine A. The relative risk was 0. 87 (95%CI0.54 to 1.38 ). The conventional formulations cyclosporine A could reduce the rate of nephrotoxicity. The relative risk was 0.69 (95 %CI0.48 to 0.95 ). There was no significant difference on the level of serum creatinine between the two groups. The weighted mean difference of lweeks, lw,l,2,3,6,12 and 24 months were 17.64 (95%CI(-98.84 to 63.56 ), -17.75 (95%CI-43.50 to 8.01 ), -21.06 (95%CI-47.87 to 5.75 ), -26.46 (95% CI-48.16 to -4.76 ), -5.00 (95%CI-11.86 to 1.86 ), -0.48 (95%CI-12.61 to 11.65 ) and 13.42 (95%CI-5.04 to 31.88 ) respectively. The conventional formulations cyclosporine A could depress the blood pressure .However it has not clinical significance .The weighted mean difference of 6, 12 and 18 months were -3.60 (95%CI -5.91 to -1.29 ), -3.60 (95%CI -5.93 to -1.27 ) and -2.50 (95% CI -4.96 to -0.04 ) respectively for systolic pressure and -2.20 (95%CI -3.74 to -0.66 ),-2.90 (95%CI-4.45 to -1.35 ) and -2.10 (95%CI -3.70 to -0.50 ) respectively for diastolic pressure. Microemulsion cyclosporine A was more effective in decreasing the incidence of acute rejection rejection than that of conventional formulations of cyclosporine A , (RR 1.24 ,95%CI 0.94 to 1.63) during 6 months ;( RR1.37 95%CI1.03 to1.82)during 12 months; (RR 1.00 ,95%CI0.56 to 1.80) during 18 months and (RR1.56 ,95%CI0.85 to 2.84) during 24 months for number of patients of acute rejection. There was no significant difference on the survival rate of patient and graft within 15 years between the two groups. The relative risk of 3,12 and 18 months were 1.00 (95%CI0.97 to 1.03), 1.01 (95%CI0.96 to 1.06)and 1.01 (95%CI1.00 to 1.03Respectively for the survival rate of patient and 1.01 (95%CI0.95 to 1.08), 1.01 (95%CI0.97 to 1.05 )and 1.00 (95%CI0.98 to 1.01 Respectively for the survival rate of grafts.Conclusion: For rejection microemulsion cyclosporine A is more effective than that of conventional formulations. But there is no significant difference in blood pressure , nephrotoxicity and the survival rate of grafts or patients.Part â…¡:Systematic review for long-term efficacy andsafety for normal dose versus withdrawal ofcyclosporine A after renal transplantationObjective: To evaluate the efficacy and safety for normal dose versus withdrawal of Cyclosporine A on transplanted renal function, blood pressure, Risk factors of cardiovascular disease, survival rate of patient and graft on stable patients after renal transplantation.Methods: Being the same as Part â… : Systematic review for efficacy and safety of microemulsion and conventional formulations for cyclosporine A after renal transplantation.Results: Thirteen studies involving 1,793 patients were included. According to the results of meta-analysis, cyclosporine A withdrawal could cut down the level of serum creatinine within 2 years comparing with cyclosporine A continuing .The weighted mean difference of 3,6, 12 and 24 months were -14.42 (95%CI-28.75 to -0.10), -10.47(95%CI-11.33 to -9.62), -20.56(95 % CI-28.88 to -12.24) and -28.00 (95 % CI-28.94 to -27.06) respectively. Cyclosporine A withdrawal could also improve the glomerular filtration rate . The weighted mean difference of 6, 12 24 and36 months were 8.00(95%CI2.31 to 13.69), 6.08 (95%CI5.80 to 6.36), 9.97 (95%CI9.66 to 10.28) and 12.12 (95%CI11.78 to 12.46) respectively. However there was no significant difference on the level of serum total cholesterol and triglyceridewithin 12 years between the two groups. The weighted mean difference of 3, 6,9, 12 24 andl44 months were 0.19(95 %CI(-0.40 to 0.78),-0.26 (95% CI-0.66 to 0.13) ,( -0.57(95%CM.10 to -0.04) , -1.55 (95%CI -1.18 to -1.92), 0.42 (95%CI-0.02 to 0.86) and -1.34 (95%CI-1.34 to 0.14) respectively for total cholesterol and the weighted mean difference of 3, 6,9, 12 and 144 months were -0.14 (95%CI(-0.35 to 0.07), -0.04 (95%CI(-0.66 to 0.58), -0.03 (95%CI(-0. 37 to 0.31), -0.60 (95%CI(-0.90 to -0.30) and -0.60 (95%CI(-1. 34 to 0.14) respectively for serum triglyceride. Cyclosporine A withdrawal could also depress the blood pressure on the renal transplant recipient. However there was no significant difference on blood pressure in the first year . The weighted mean difference of 6, 12, 24 60 and 120 months were -4.00 (95%CI-8.66 to 0.66), 0.00 (95%CI-2.94 to 2.94)), -6.00 (95% CI-8.55 to -3.45), -7.00 (95%CI-9.67 to -4.33)and -3.00(95%CI-4.60 to -1.40) respectively for diastolic pressure and 1.00 (95%CI-8.36 to 10.36), -2.00(95 %CI -9.74 to 5.74), -4.00 (95%CI-10.94 to 2.94), -2.00 (95%CI-10.81 to 6.81) and -10.00 (95%CI-18.28 to -1.72) respectively for systolic pressure. Cyclosporine A withdrawal was more effective in decreasing the incidence of acute rejection rejection than that of normal dose of cyclosporine A , (RR 3.22 ,95%CI 1.61 to 6.45) during 6 months; ( RR2.02 95%CI1.02 to 4.01)during 12 months for number of patients for acute rejection. But there was no significant difference in chronic rejection . The relative risks of 6 and 12 months were (RR1.80 ,95%CI 0.97 to 3.33) and (RR 0.81 ,95%CI 0.61 to 1.08). According to the results of meta-analysis, we had also found that there was no significant difference on the survival rate of patient and graft within 15 years between the two groups. The relative risk of 12,60,120 and180 months were 0.99 (95%CI0.98 to 1.01), 1.03 (95%CI0.96 to 1.10), 1.16 (95%CI0.98 to 1.37 )and 0.90 (95%CI0.71 to 1.15)respectively for the survival rate of patient and 1.00 (95%CI0.98 to 1.02), 1.04 (95%CI0.96 to 1.12 ), 1.17 (95 % CI0.97 to 1.42)and 1.08 (95 % CI0.82 to 1.42)respectively for the survival rate of grafts.Conclusion: For blood pressure and the level of serum creatinine, cyclosporine A withdrawal is more effective than that of cyclosporine A. However there is no significant difference in the blood fat ,chronic rejection and the survival rate of grafts or patientsPart â…¢:Systematic Review for comparison tacrolimus and cyclosporine A after renal transplantationObjective: To evaluate the effectiveness of tacrolimus and cyclosporine A on acute rejection, chronic rejection and survival rate of patient and graft after renal transplantation.Methods: Being the same as Part I : Systematic review for efficacy and safety of microemulsion and conventional formulations for cyclosporine A after renal transplantation.Results: Eighteen studies involving 3,738 patients were included. Tacrolimus was more effective in decreasing the incidence of acute rejection and chronic rejection than that of cyclosporine A, (RR 0.65 ,95%CI 0.56 to 0.75) during 6 months and (0.70 95%CI0.54 to 0.92)during 12 months for number of patients of acute rejection. The relative risk was 0.65 (95% CI 0.47 to 0.89) for number of patients of chronic rejection. Tacrolimus can also reduce the severity of acute rejection. The relative risk of pathologic grade Banff â… and Banff (â…¡ +â…¢) were 1.64 (95% CI 1.08 to 2.49) and 0.75 (95 %CI0.63 to 0.89) respectively. But there was no significant difference on the survival rate of patient and graft within 5 years between the two groups. The relative risk of 6,12,24,36 and 60 months were 1.01 (95%CI 0.99 to 1.02), 1.00 (95%CI0.99 to 1.02) , 1.01 (95%CI0,97 to 1.05) , 1.00 (95%CI0.97 to 1.03) and 0.97 (95%CI0,88 to 1.07) respectively for the survival rate ofpatient and 1.04 (95%CI 1.01 to 1.02), 1.03 (95%CI1.00 to 1.06) , 0.99(95%CI0,91 to 1.07) , 1.04 (95%CI0.99 to 1.09) and 1.04 (95%CI0,90 to1.21) respectively for the survival rate of grafts. The relative risk of 24,36 and60 months for the survival rate of graft were 0.99 (95 %CI0,91 to 1.07) , 1.04(95%CI0.99 to 1.09) and 1.04 (95%CI0,90 to 1.21) respectively.Conclusion: For acute rejection and chronic rejection, tacrolimus is more effective than cyclosporine A. However there is no significant difference in the survival rate of grafts or patients.
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