***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
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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 BACKGROUND Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients . This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens . METHODS We r and omly assigned 1645 renal-transplant recipients to receive st and ard-dose cyclosporine , mycophenolate mofetil , and corticosteroids , or daclizumab induction , mycophenolate mofetil , and corticosteroids in combination with low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus . The primary end point was the estimated glomerular filtration rate ( GFR ) , as calculated by the Cockcroft-Gault formula , 12 months after transplantation . Secondary end points included acute rejection and allograft survival . RESULTS The mean calculated GFR was higher in patients receiving low-dose tacrolimus ( 65.4 ml per minute ) than in the other three groups ( range , 56.7 to 59.4 ml per minute ) . The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus ( 12.3 % ) than in those receiving st and ard-dose cyclosporine ( 25.8 % ) , low-dose cyclosporine ( 24.0 % ) , or low-dose sirolimus ( 37.2 % ) . Allograft survival differed significantly among the four groups ( P=0.02 ) and was highest in the low-dose tacrolimus group ( 94.2 % ) , followed by the low-dose cyclosporine group ( 93.1 % ) , the st and ard-dose cyclosporine group ( 89.3 % ) , and the low-dose sirolimus group ( 89.3 % ) . Serious adverse events were more common in the low-dose sirolimus group than in the other groups ( 53.2 % vs. a range of 43.4 to 44.3 % ) , although a similar proportion of patients in each group had at least one adverse event during treatment ( 86.3 to 90.5 % ) . CONCLUSIONS A regimen of daclizumab , mycophenolate mofetil , and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function , allograft survival , and acute rejection rates , as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with st and ard-dose cyclosporine without induction . ( Clinical Trials.gov number , NCT00231764 [ Clinical Trials.gov ] . ) 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 . Long-term maintenance immunosuppression with cyclosporine ( CsA ) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile . Several nonr and omized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil ( MMF ; CellCept ) . Methods . A r and omized , controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF ( 2 g/day ) , CsA ( Neoral ) , and corticosteroids .  The primary endpoint was creatinine clearance at 6 months after complete withdrawal . Results . In the intent-to-treat population , CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol ( −0.3 mmol/L , P = 0.02 ; −0.4 mmol/L , P = 0.015 ) . There was a trend toward improved creatinine clearance ( 4.5 mL/min , P = 0.16 ) and serum creatinine ( −1 vs. + 4 & mgr;mol/L , P = 0.34 ) . In the per- protocol population , which excluded patients with acute rejections , the improvements in creatinine clearance and serum creatinine were statistically significant ( 7.5 mL/min , P = 0.02 ; −11 vs. + 4 & mgr;mol/L , P = 0.0003 ) . Reversible acute rejections , the majority of which were mild , occurred in nine CsA withdrawal versus two CsA continuation patients ( 10.6 % vs. 2.4 % of each group , P = 0.03 ) , with no graft loss . Conclusion . Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections , without graft loss Maintenance immunosuppression with cyclosporine ( CsA ) is associated with nephrotoxicity , hyperlipidemia , and hypertension . This long-term study ( core study + 4 yr of follow-up ) investigated the long-term efficacy and safety of CsA withdrawal from a mycophenolate mofetil (MMF)-based regimen . Seventy-seven patients were maintained on CsA , MMF , and steroids ( CsA-MMF group ) , and 74 were given a CsA-free regimen of MMF and steroids ( MMF group ) .  Serum creatinine and creatinine clearance were measured at 6-month intervals . Patient and graft survival , acute rejection episodes , malignancies , BP , and lipid profile were also recorded . At 5 yr , patient and graft survival was 93 and 88 % , respectively , for the MMF group and 95 and 92 % , respectively , for the CsA-MMF group . During follow-up , seven MMF patients experienced acute rejection episodes compared with one CsA-MMF patient ( P = 0.0283 ) . Nine grafts were lost to chronic rejection in the MMF group versus three in the CsA-MMF group . No demographic or immunologic characteristics were associated with acute or chronic rejection in the MMF group , but the doses of both MMF and steroids decreased significantly between 1 and 5 yr . The MMF group showed a trend toward improved creatinine clearance ( 67.4 versus 61.7 ml/min ; P = 0.0500 ) . Withdrawal of CsA from an MMF-containing immunosuppressive regimen result ed in an increased risk for acute rejection episodes and graft loss as a result of rejection throughout the 5-yr study period . The creatinine clearance-confirmed improvement in renal function observed at year 1 was maintained at 5 yr BP and cholesterol levels were well controlled in both groups 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 . We report the two-year follow-up of a trial comparing the three-month postgraft discontinuation of either cyclosporine ( CsA ) or mycophenolate mofetil ( MMF ) from a triple-drug regimen after de novo renal transplantation . Methods . One hundred and eight patients were enrolled in this study and r and omized to be withdrawn from CsA ( MMF group , n=54 ) or MMF ( CsA group , n=54 ) . Results . Despite an increased risk of acute rejection and a lower , but nonsignificant , two-year graft survival , CsA withdrawal induced a sustained improvement of the renal function . At one year , the chronic allograft damage index was similar in both the MMF and CsA groups . However , CsA elimination result ed in a higher incidence of C4d deposits , irrespective of the occurrence of a prior acute rejection . While this finding could suggest a risk of chronic rejection in the MMF group , the outcome did not appear to be related to the 
    Output:
    
There were no significant differences in mortality , malignancy or incidence of infections .
CONCLUSIONS CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients .
Improvements in short-term graft function , and possibly graft survival , are achievable .
Longer term studies are needed to substantiate the short-term benefits , and refining elective CNI elimination protocol s may help to reduce the risk of rejection