***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Long‐term use of calcineurine inhibitors ( CNIs ) may contribute to the development of chronic allograft dysfunction ( CAD ) . We investigate the impact of the introduction of MMF combined with cyclosporine ( CsA ) 50 % dose reduction . An open , r and omized , controlled , multicenter , prospect i ve study was conducted in 103 patients , receiving a CsA‐based therapy with a serum creatinine between 1.7–3.4 mg/dL , more than 1 year after transplantation . They were r and omized to receive MMF with half dose of CsA ( MMF group ) or to continue their maintenance CsA dose ( control group ) . A total of 96 weeks after r and omization , the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group ( positive slope ) vs. the control group ( negative slope ) , 4.2 × 10−4 vs. −3.0 × 10−4 , respectively ( p < 0.001 ) . Concurrently , the absolute renal function improved significantly in the MMF group . No episode of biopsy‐proven acute rejection occurred . One patient in each group lost his graft because of biopsy‐proven chronic allograft nephropathy . There was a significant decrease of triglycerides level in the MMF group . Anemia and diarrhea were statistically more frequent in the MMF group Introduction . The purpose of this study was to evaluate early cyclosporine ( CsA ) withdrawal from a sirolimus (SRL)-CsA-steroid ( ST ) regimen . Methods . Within 48 hr after transplantation , 525 primary ( 90 % ) or secondary ( 10 % ) renal allograft recipients with cadaveric ( 89 % ) or living ( 11 % ) donors received 2 mg of SRL ( troughs > 5 ng/mL ; immunoassay ) , CsA , and ST .  Those eligible ( 430 ) were r and omly assigned ( 1:1 ) at 3 months ± 2 weeks to remain on triple-drug therapy ( SRL-CsA-ST group ) or to have CsA withdrawn and SRL trough concentrations targeted to 20 to 30 ng/mL ( SRL-ST group ) until month 12 , and 15 to 25 ng/mL thereafter . Results . At 24 months , there were no statistically significant differences in patient survival ( 94.0 % vs. 95.3 % ) , graft survival ( 91.2 % vs. 93.5 % ) , acute rejection after r and omization ( 5.1 % vs. 9.8 % ) or discontinuations ( 34 % vs. 33 % ) for SRL-CsA-ST versus SRL-ST , respectively . Serum creatinine level was significantly better in patients who had CsA withdrawn ( 167 vs. 128 & mgr;mol/L , P < 0.001 ) , as was the slope of 1/creatinine . Similarly , systolic blood pressure was lower in patients who had CsA withdrawn ( 141 vs. 134 mm Hg , P < 0.001 ) . High-density lipoprotein cholesterol was significantly higher in the SRL-ST group , whereas total cholesterol , low-density lipoprotein cholesterol , and triglyceride levels were not significantly different . Hypertension , creatinine increase , abnormal kidney function , toxic nephropathy , edema , hyperuricemia , cataracts , Herpes zoster , and malignancy were reported significantly more often in patients continuing CsA.  Thrombocytopenia , hypokalemia , abnormal liver function tests , abnormal wound healing , ileus , and pneumonia were reported significantly more frequently with SRL-ST . Conclusion . Data at 2 years confirm that early CsA withdrawal followed by an SRL-ST maintenance regimen results in long-term improvement in both renal function and blood pressure , without increased risk of graft loss or late acute rejection Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival , but their use has been implicated in the development of chronic nephrotoxicity . We performed a prospect i ve , r and omized trial in kidney transplantation comparing sirolimus‐MMF‐prednisone to tacrolimus‐MMF‐prednisone .  Eighty‐one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled ( mean follow‐up = 33 months ; range 13–47 months ) . At 1 year , patient survival was similar in the groups ( 98 % with sirolimus , 96 % with tacrolimus ; p = 0.42 ) as was graft survival ( 94 % sirolimus vs. 92 % tacrolimus , p = 0.95 ) . The incidence of clinical acute rejection was 10 % in the tacrolimus group and 13 % in the sirolimus group ( p = 0.58 ) . There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year ( 61 ± 19 mL/min vs. 63 ± 18 mL/min , p = 0.57 ) or 2 years ( 61 ± 17 mL/min vs. 61 ± 19 mL/min , p = 0.84 ) . At 1 year , chronicity using the Banff schema showed no difference in interstitial , tubular or glomerular changes , but fewer chronic vascular changes in the sirolimus group . This study shows that a CNI‐free regimen using sirolimus‐MMF‐prednisone produces similar acute rejection rates , graft survival and renal function 1–2 years after transplantation compared to tacrolimus‐MMF‐prednisone Background . This study determined whether cyclosporine A (CsA)-treated  renal allograft recipients with deteriorating renal function ( “ creeping creatinine ” ) secondary to chronic allograft nephropathy ( CAN ) benefit from the addition of mycophenolate mofetil ( MMF ) to their immunosuppressive regimen , followed by withdrawal of CsA. Methods . In a controlled , open , multicenter study , CsA-treated renal allograft recipients with progressively deteriorating renal function were r and omized to have their CsA discontinued with the concomitant addition of MMF to their regimen ( group A ) or to continue treatment with CsA ( group B ) . The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine ( SCr ) , as evidence d by a flattening or positive slope of the 1/SCr plot and no graft loss . Secondary endpoints included the incidence of acute rejection , graft and patient survival , and changes in selected metabolic parameters . Results . The response rate in the primary intent-to-treat population ( n=122 ) was 58 % ( 36/62 ) in group A versus 32 % ( 19/60 ) in group B ( P=0.0060 ) . The corresponding percentages of responders in the per- protocol population ( n=107 ) were 60 % ( 36/60 ) and 26 % ( 12/47 ) , respectively ( P=0.0008 ) . There were no acute rejections in group A during the study period . Patients in this group also experienced a significant decrease in total cholesterol . Conclusions . In patients with progressively deteriorating renal function secondary to CAN , addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection BACKGROUND Tacrolimus and ciclosporin might have different effects on intra-renal fibrosis and allograft function in chronic allograft nephropathy ( CAN ) . It is difficult to predict the response to calcineurin inhibitor minimization in patients with CAN . METHODS This prospect i ve r and omized study compared ciclosporin A (CsA)-to-tacrolimus conversion ( group A , target tacrolimus trough level 6 - 8 ng/ml ) vs CsA minimization ( group B , target CsA trough level 80 - 100 ng/ml ) with regard to efficacy and safety in patients with CAN and deteriorating allograft function . The primary efficacy endpoint was improvement in the slope of inverse serum creatinine ( 1/SCr ) vs time plot . RESULTS There were 34 evaluable patients ( n=16 in group A ; n=18 in group B ) , with similar baseline characteristics . Both groups reached target drug levels after a 3-month run-in period . Over the ensuing 12 months , nine ( 56.3 % ) subjects in group A and 10 ( 55.6 % ) in group B reached the primary end point ( P=0.968 ) . Both groups showed considerable improvement in the slope of 1/SCr vs time plot . There was no significant difference in the slope between groups before and after intervention . Graft survival was 87 % in group A and 100 % in group B ( P=0.121 ) . Acute rejection was encountered in two group A subjects . There was no significant change or difference in blood glucose , lipids , and blood pressure between groups . CONCLUSION Our results suggest that in patients with CAN and deteriorating allograft function , CsA-to-tacrolimus conversion or CsA minimization achieved comparable efficacies in retarding the decline of graft function . Such contention may be biased by the low patient number . Further studies with a larger cohort are needed for validation BACKGROUND This study was conducted to assess the effect of immunosuppression conversion on progression of chronic allograft nephropathy ( CAN ) . METHODS Forty-two cyclosporin-treated renal transplant recipients were studied . Patients were included if they had a negatively sloping reciprocal of creatinine vs time ( ROCT ) plot for > 6 months and biopsy-proven CAN . Patients were excluded if they had previously been treated with tacrolimus/mycophenolate mofetil ( MMF ) or their serum creatinine was > 400 micromol/l . Subjects were r and omly treated with either : ( A ) MMF/reduced dose cyclosporin [ MMF for azathioprine 0.5 - 1.0 g bd ; cyclosporin trough level ( C(0 ) ) : 75 - 100 ng/ml ] ; ( B ) tacrolimus for cyclosporin ( C(0 ) : 5 - 10 ng/ml ) ; or ( C ) continuation of st and ard therapy .  Glomerular filtration rate ( GFR ) was measured at baseline and after 6 months . RESULTS Two patients started dialysis within 6 months ( one each from groups A and B ) . One patient in group A was intolerant of MMF , six others reported gastrointestinal symptoms and three developed anaemia . Cyclosporin dose was reduced by 24 % [ interquartile range ( IQR ) : 14 - 27 % ] in group A [ end-of- study C(0 ) : 99 ng/ml ( IQR : 90 - 113 ng/ml ) ] . In group B , the end-of- study tacrolimus  C(0 ) was 7 ng/ml ( 5 - 9 ng/ml ) . The end-of- study cyclosporin C(0 ) in group C was 163 ng/ml ( 145 - 215 ng/ml ) . Comparison of ROCT slopes before and after intervention revealed a treatment advantage for group A ( P<0.05 ) . The GFR analysis was supportive ( P = 0.05 ) . When patients with GFR < 20 ml/min/1.73 m(2 ) at enrollment were excluded from the analysis , the treatment advantage for group A reached statistical significance ( n = 27 , P<0.05 ) . CONCLUSIONS MMF/reduced dose cyclosporin is superior to tacrolimus-for-cyclosporin and st and ard dose cyclosporin in patients with CAN , at least in the short term . The cyclosporin dose reduction component is likely to be of particular importance . Other findings suggest that early intervention is beneficial BACKGROUND Renal transplantation is the st and ard of care for patients with end-stage renal disease . Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival , it is associated over the long term with high rates of death and graft loss , owing in part to the adverse renal , cardiovascular , and metabolic effects of these agents . The use of potentially less toxic agents , such as belatacept , a selective blocker of T-cell activation , may improve outcomes . METHODS We r and omly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine . All patients received induction therapy with basiliximab , mycophenolate mofetil , and corticosteroids .  The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months ( with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent ) . RESULTS At six months , the incidence of acute rejection was similar among the groups : 7 percent for intensive belatacept , 6 percent for less-intensive belatacept , and 8 percent for cyclosporine . At 12 months , the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was 
    Output:
    
Results varied between studies but suggested that CNI withdrawal is safe and that conversion to MMF or Rapa may be beneficial .
The review did not result in a consensus regarding the management of CAN and CAD .