***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND Acute rejection episodes after renal transplantation are an important clinical challenge , despite use of multidrug immunosuppressive regimens . We did a prospect i ve , multicentre , r and omised , double-blind trial to investigate the impact of the addition of sirolimus , compared with azathioprine , to a cyclosporin and prednisone regimen . METHODS 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were r and omly assigned , after transplantation , sirolimus  2 mg daily ( n=284 ) or 5 mg daily ( n=274 ) , or azathioprine ( n=161 ) . We assessed the primary composite endpoint of efficacy failure , occurrence of biopsy-confirmed acute rejection episodes , graft loss , or death , and various secondary endpoints that characterise these episodes at 6 months and 12 months . Analyses were done by intention to treat . FINDINGS The rate of efficacy failure at 6 months was lower in the two sirolimus groups ( 2 mg 18.7 % , p=0.002 ; 5 mg 16.8 % , p<0.001 ) than in the azathioprine group ( 32.3 % ) . The frequency of biopsy-confirmed acute rejection episodes was also lower ( 2 mg 16.9 % , p=0.002 ; 5 mg 12.0 % , p<0.001 ; azathioprine 29.8 % ) . At 12 months , survival was similar in all groups for grafts ( 97.2 % , 96.0 % , and 98.1 % ) and patients ( 94.7 % , 92.7 % , and 93.8 % ) . Patients on sirolimus  showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grade s of rejection episodes and related antibody treatment , compared with the azathioprine group . Rates of infection and malignant disorders were similar in all groups . INTERPRETATION Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications . Further studies are needed to establish the optimum doses for the combined regimen Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function . The aim of this study was to compare the effects of tacrolimus ( Tac ) and cyclosporine microemulsion ( CsA ) based immunosuppressive protocol s using protocol biopsies from well-functioning renal allografts . 35 consecutive renal transplant patients were r and omized to Tac ( n : 17 ) versus CsA ( n : 18 ) treatment arms . Patient age and sex , donor type and age , histocompatibility , cold ischemia time and prior delayed graft function were similar between the two groups . Treatment protocol consisted of prednisolone , azathioprine and Tac or CsA. Biopsies performed on the third , sixth and twelfth months were blindly evaluated by the same pathologist . The incidences of acute rejection ( AR ) episodes among CsA vs Tac groups were 33 % vs 29 % , respectively ( NS ) . The Creatinine level was lower in Tac than CsA , although it was not significant ( Table ) . Sub clinical AR and sub clinical chronic allograft nephropathy were detected on protocol biopsies in 3 ( 2 CsA , 1 Tac ) and 12 ( 7 CsA , 5 Tac ) patients , respectively . Acute lesion score at the third month PBx was significantly lower in the Tac group ( p < 0.05 ) . Chronic lesion scores in all biopsies were lower in the Tac group , although not significantly . The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group This review focuses upon the sirolimus-based cyclosporine elimination studies and the light they shed on choice of the best long-term immunosuppressive strategy for managing the balance between prevention of loss of grafts from antigen specific immune responses or from chronic nephrotoxicity . The underlying strategy of both cyclosporine elimination studies was to treat patients with a uniform therapy for the first 3 months and then wean off the cyclosporine therapy in one cohort . The Phase II study was conducted in 246 recipients in 17 centers in the USA and Europe . Thus 97 patients were treated with full-dose cyclosporine , fixed-dose sirolimus and corticosteroids , and 100 patients received reduced-dose cyclosporine and trough concentration controlled sirolimus with corticosteroids until 3 months when the dose of cyclosporine was tapered progressively . The phase III study was undertaken in 525 patients in 57 centers in Australia , Canada and Europe with r and omization for cyclosporine elimination undertaken at 3 months and implemented over the next 4 - 6 weeks . The primary outcome of renal function was better in the elimination arms of both studies and , in the phase III study , continued to improve for up to 2 years . Both studies demonstrated better renal function , equivalent patient and graft survival and no difference in acute rejection rates . These studies have shown that one of the successful strategies for improving the longer term graft survival rates includes the continuous use of sirolimus and steroids , without calcineurin inhibitors BACKGROUND In previous comparative studies tacrolimus was superior to the st and ard formulation of ciclosporin in preventing acute rejection  after renal transplantation . We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre r and omised trial . METHODS The 6-month open study involved 560 patients in 50 European centres . 287 patients were r and omly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids .  The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8 - 10 mg/kg for ciclosporin . The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event . FINDINGS The two study groups were similar in terms of baseline characteristics . Three patients did not receive study treatment or did not undergo transplantation ( one tacrolimus , two ciclosporin ) . The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion ( 56 patients [ 19.6 % ] vs 101 [ 37.3 % ] ; 17.7 % difference [ 95 % CI 10.3 - 25.1 ] ; p<0.0001 ) . Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus ( 27 [ 9.4 % ] vs 57 [ 21.0 % ] ; 11.6 % difference [ 5.7 - 17.5 ] ; p<0.0001 ) . Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 ( 0.3 % ) tacrolimus-group patients and 27 of 271 ( 10.0 % ) ciclosporin-group patients ( p<0.0001 ) . There were no significant differences in survival of patients or grafts or in renal function . The overall frequency of adverse events was similar in the two groups , though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group . INTERPRETATION Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile BACKGROUND Daclizumab ( Zenapax , Roche Pharmaceuticals ) , a humanized monoclonal antibody directed against the alpha chain of the interleukin 2 receptor , has been shown to reduce the incidence of acute rejection at 6 months after renal transplantation in two phase III clinical trials . This report presents the combined 1- and 3-year outcomes of kidney transplant recipients who participated in these two phase III clinical trials . METHODS Data from two multicenter , r and omized , placebo-controlled trials were evaluated with regard to graft survival , patient survival , incidence of malignancies ( including lymphoma ) , renal function ( serum creatinine and glomerular filtration rate [ GFR ] ) , and current maintenance immunosuppressive regimen . In addition , the impact of acute rejection and acute rejection requiring treatment with antilymphocyte therapy upon 3-year graft survival was evaluated . Daclizumab was compared to placebo on a background of cyclosporine ( CsA ) , azathioprine , and corticosteroids ( triple therapy , TT ) or CsA and corticosteroids ( double therapy , DT ) . RESULTS Treatment with daclizumab in the pooled analysis demonstrated a significant reduction in the incidence of biopsy-proven acute rejection episodes at 12 months posttransplant ( 43 % vs. 28 % , P<0.001 ) . The 3-year graft survival was not significantly different between placebo and daclizumab-treated patients in the TT trial ( 83 % vs. 84 % ) or in the DT trial ( 78 % vs. 82 % ) . Pooled patient survival was excellent in both placebo- ( 91 % ) and daclizumab- ( 93 % ) treated patients . The incidence of malignancies or posttransplant lymphoproliferative disorder ( PTLD ) in placebo- versus daclizumab-treated groups was comparable in both clinical trials . Renal function was similar between placebo- and daclizumab-treated groups in both the TT and DT trials . The occurrence of delayed graft function , acute rejection requiring antilymphocyte therapy at 6 months , and acute rejection at 12 months posttransplant were associated with decreased graft survival rates at 3 years posttransplant . CONCLUSIONS The beneficial effect of daclizumab prophylaxis upon the incidence of acute rejection after renal transplant with TT or with DT was not associated with adverse clinical sequelae , including the development of PTLD , at 3 years posttransplant . There was no beneficial effect of daclizumab on graft survival at 3 years , but the trial was inadequately powered to detect this . Both studies showed excellent graft and patient survival at 3 years Background . Mycophenolate mofetil (MMF)-based immunosuppression has reduced the acute rejection rate in adults and in children in the early posttransplantation period . Three-year posttransplantation results have been reported for adults but not for children thus far . In the present open-labeled study , patients 18 years old and younger were evaluated prospect ively for up to 3 years after renal transplantation ( RTX ) . Methods . Eighty-six patients receiving MMF in combination with cyclosporine and prednisone without induction were evaluated for patient survival , transplant survival , renal function , arterial blood pressure , adverse events , and opportunistic infections . These patients were compared with a historic control group ( n=54 ) receiving azathioprine ( AZA ) instead of MMF . Results . Patient survival after 3 years was 98.8 % in the MMF group and 94.4 % in the AZA group ( NS ) . Intent-to-treat analysis of graft survival demonstrated superiority for MMF ( 98 % vs. 80 % ; P<0.001 ) . Cumulative acute rejection episodes occurred in 47 % of patients in the MMF group versus 61 % in the AZA group ( P<0.05 ) . Renal function was not significantly different , neither after 3 years nor in the long-term calculation . Antihypertensive medication was administered to 73 % to 84 % of patients , similar in both groups . Opportunistic infections were recorded only for MMF .  Infection rates were comparable to those reported in adults . Conclusions . These results suggest that MMF is safe and beneficial as a longer term maintenance immunosuppressive drug in children and adolescents Objective : To study the efficacy and safety profile of Simulect , anti-IL-2R monoclonal antibody , and prevent the acute rejection in renal allograft recipients . Methods : 46 patients were treated with Neoral-based immunosuppressive agents combined with or without Simulect  in March 1999-October 2002 in our organ transplant center . The 46 patients were classified into two groups , group Simulect and group control r and omly . The all patients in both groups received Neoral , Azatheoprine and steroid conventionally , but the patients in group Simulect were given Simulect additionally with the first dose of Simulect 20mg,2 hours preoperatively and the second dose of 20 mg 4 days postoperatively . Thereafter , acute rejection , dosage of Neoral , steroids and Azatheoprine as well as the toxicity of these agents and Simulect were closely monitored . In addition , the trough level of CsA in whole blood , liver and renal functions were also monitored . Results : In 8 weeks post-transplantation,3 cases of group control recipients experienced 4 episodes of acute allograft rejection , but none of group Simulect recipients had it(P0.01).No patients in both groups were associate with toxicity , such as cytokin release syndrome , CMV infection and post-transplantation 
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RESULTS For the addition of basiliximab , one unpublished paediatric r and omised control trial ( RCT ) , reported that the addition of basiliximab to tacrolimus-based triple therapy ( BTAS ) failed to significantly improve 6-month biopsy-proven acute rejection ( BPAR ) , graft function , graft loss and all-cause mortality .
No significant difference between groups was seen in 6-month or 1-year or longer graft loss , all-cause mortality and side-effects .
In a meta- analysis of adult RCTs , the addition of basiliximab to a ciclosporin , azathioprine and steroid regimen ( CAS ) significantly reduced short-term BPAR .
There was evidence , particularly in children , that in comparison with ciclosporin , tacrolimus may reduce long-term graft loss , although there is no benefit on total mortality .
The total level of withdrawal in children was reduced in children receiving tacrolimus .
Adult RCTs showed an increase in post-transplant diabetes mellitus with tacrolimus .
There was evidence , particularly in children , that in comparison with azathioprine , tacrolimus may reduce long-term graft loss , although there is no benefit on total mortality .
There was an increase in the level of cytomegalovirus infection with MMF , although the overall level of withdrawal due to adverse events was not different to that of azathioprine-treated adults .
The addition of basiliximab and that of daclizumab to CAS was found to increase quality -adjusted life-years ( QALYs ) and decreased overall costs , a finding that was robust to sensitivity analyses .
The incremental cost-effectiveness ratio ( ICER ) of replacing ciclosporin with tacrolimus was highly sensitive to the selection of the hazard ratio for graft loss from acute rejection , dialysis costs and the incorporation ( or not ) of side-effects .
In general , compared with a regimen of ciclosporin , azathioprine and steroid , the newer immunosuppressive agents consistently reduced the incidence of short-term biopsy-proven acute rejection .
However , evidence of the impact on side-effects , long-term graft loss , compliance and overall health-related quality of life is limited .
Both the addition of daclizumab and that of basiliximab were found to be dominant strategies , that is , regarding cost savings and increased QALYs .
The incremental cost-effectiveness of tacrolimus relative to ciclosporin was highly sensitive to key model parameter values and therefore may well be a cost-effective strategy .
The incremental cost-effectiveness of MMF compared with azathioprine , although also sensitive to model parameter , was unattractive .