***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: INTRODUCTION The EuroTransplant " old to old " program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years . The compromised function of these organs makes it a priority to preserve their initial kidney function . HYPOTHESIS Calcineurin-sparing protocol s using anti-IL-2 receptor ( IL-2R ) antibody induction ( Simulect ) may benefit initial kidney function in these patients , as assessed by the rates of delayed graft function and of rejection during the first month after transplant . PATIENTS AND METHODS A cohort of 15 consecutive elderly patients were prospect ively compared with 30 cadaveric kidney transplants in younger recipients . Study patients were induced with Simulect ( 20 mg , 30 minutes before reperfusion and 4 days after transplantation ) and steroids , delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus ( trough 8 to 12 ) , mycophenolats mofetil ( MMF , 1 g/d ) , and an identical taper of steroids . The analysis compared donor and recipient ages , mean cold ischemic time , incidence of initial kidney function ( diuresis in the first 24 h ) serum creatinine levels , glomerular filtration rate ( GFR ) , number of dialysis sessions , and rejection rate in the two groups . RESULTS Except for the donor and recipient ages ( 72 vs 54 in donors , and 67 versus 52 years in recipients ) , no significant differences were observed between the groups among the rates of acute rejection ( 6.6 % vs 13.2 % ) , delayed graft function ( 13.2 % required dialysis ) , or infection ( 6.6 % ) . Within 1 month all 45 grafts showed primary function with equal creatinine levels ( mean 1.65 ) . CONCLUSIONS Calcineurin-free protocol s using IL-2 therapy as the initial suppression allow patients in the " old to old " ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists Background . Two open-label studies demonstrated that conversion from mycophenolate mofetil ( MMF ) to enteric-coated mycophenolate sodium ( EC-MPS ) significantly reduces gastrointestinal ( GI ) symptom burden and improves GI-specific health-related quality of life . Using a r and omized design , this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment . Methods . In this 4-week , multicenter , r and omized , prospect i ve , double-blind , parallel-group trial , renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitor±corticosteroids  were r and omized to an equimolar dose of EC-MPS+MMF placebo or continue on their MMF-based regimen+EC-MPS placebo . The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3 . Results . Three hundred ninety-six patients ( EC-MPS group : n=199 ; MMF group : n=197 ) were included . A greater proportion of EC-MPS patients ( 62 % ) reached the primary efficacy outcome compared with MMF patients ( 55 % ) ; however , the difference was not statistically significant ( P=0.15 ) . EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients . Within the subgroups of patients with diabetes , patients transplanted 6 to 12 months of study enrollment , and patients on steroids , a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome . Conclusions . Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms , particularly in patients with indigestion , diabetes , on steroids , and in patients converted between 6 and 12 months posttransplantation This study was design ed to investigate the effect of tacrolimus ( FK506 ) and of cyclosporine ( CsA ) on tubular function in renal graft recipients . Patients were r and omised after renal transplantation to immunosuppressive treatment with FK506 ( n = 8) or CsA ( n = 8) . Patients had a mean age of 45.7 + /- 3.4 yr ; there was no difference in age , sex , HLA status or CMV mismatches . Neither was there any difference in the frequency of episodes of acute kidney failure between the groups , nor was there a significant difference in the frequency of episodes of kidney rejection within the first year . The mean FK506 level at the time lay at 14.7 + /- 14.4 ng/mL whole blood , and the mean CsA level at the time of study was 162 + /- 25 ng/mL whole blood . We performed renal function studies 6 months after transplantation : CIn , CPAH , NaHCO3 loading , and Na2SO4 loading . There was no significant impairment of GFR in patients treated with FK506 with 53.6 + /- 2.5 mL/min as compared to 58 + /- 6 mL in group 2 . Plasma renin activity ( 0.6 + /- 0.4 ng/mL vs 2.3 + /- 3 ; p < 0.01 ) and aldosterone ( 69 + /- 17 vs 157 + /- 28.2 pg/mL ; p < 0.05 ) were significantly decreased during treatment with FK506 .  Fractional HCO3 excretion was low in both groups , indicating that bicarbonate reabsorption in the proximal nephron was unimpaired . Distal renal tubular acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2 . Potassium levels were slightly increased in patients treated with FK506 ( 5.4 + /- 0.2 mmoL/L ) as compared to cyclosporine ( 4.9 + /- 0.3 mmoL/L ; p < 0.05 ) . Distal hydrogen ion secretion , evaluated by the ability to increase urinary pCO2 in a highly alkaline urine , was impaired in patients treated with FK506 ( U-B pCO2 : 16.1 + /- 4 vs 36 + /- 5.8 ; p < 0.05 ) as compared to patients treated with CsA. The maximum acidification capability ( NAE ) was slightly lowered during therapy with FK506 ( 67.5 + /- 11.8 versus 86.6 + /- 16.5 mumoL/min , ns ) . We conclude that FK506 administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubules . This defect was disclosed by the finding of a subnormal pCO2 in a highly alkaline urine . These results show that FK506 is able to induce distal tubular acidosis . Distal tubular acidosis is part of FK506 induced nephrotoxicity , the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be further eluci date 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 Background No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant ( RTx ) patients . Methods This 12-month , multicenter , open-label study r and omized ( 1:1 ) 122 Japanese de-novo RTx patients to either an everolimus regimen  ( 1.5 mg/day starting dose ( target trough : 3 to 8 ng/ml ) + reduced-dose cyclosporine ) or a mycophenolate mofetil ( MMF ) regimen  ( 2 g/day + st and ard dose cyclosporine ) . All patients received basiliximab and corticosteroids . Key endpoints at month 12 were composite efficacy failure ( treated biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) and renal function ( estimated glomerular filtration rate ; Modification of Diet in Renal Disease-4 ) . Results Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study ( 52 % reduction at month 12 ) . Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF ( 11.5 % vs. 11.5 % ) . The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group ( P = 0.063 ) . Overall , the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments . The everolimus group had a higher incidence of wound healing events and edema , whereas a higher rate of cytomegalovirus infections was reported in the MMF group . Conclusions This study confirmed the efficacy of everolimus 1.5 mg/day ( target trough : 3 to 8 ng/ml ) in Japanese RTx patients for preventing acute rejection , while allowing for substantial cyclosporine sparing . Renal function and safety findings were comparable with previous reports from other RTx population s . Trial registration Clinical Trials.gov number : Background The once-daily ( QD ) , prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily ( BD ) tacrolimus . Treatment nonadherence in transplant recipients has been associated with poor graft outcomes . Methods This open-label , parallel-group study r and omized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day ( Arm 1 ; n=309 ) , QD 0.2 mg/kg per day ( Arm 2 ; n=302 ) , QD 0.3 mg/kg per day ( Arm 3 ; n=304 ) all with mycophenolate mofetil and corticosteroids  ( tapered ) over 24 weeks , or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil , basiliximab , and corticosteroids given only perioperatively ( Arm 4 ; n=283 ) . The primary composite endpoint ( efficacy failure ; per protocol set ) was defined as graft loss , biopsy-confirmed acute rejection , or graft dysfunction at week 24 . Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m2 . The prespecified noninferiority margin was 12.5 % . Results The per protocol set included 976 patients : 237 , 263 , 246 , and 230 patients in Arms 1 to 4 , respectively . Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1 ; Kaplan – Meier estimates of efficacy failure were 42.2 % and 40.6 % , respectively ( difference , −1.6 % ; 95 % confidence interval [ CI ] , −12.2 % to 9.0 % ) . Noninferiority to Arm 1 was not confirmed for Arm 3 ( difference , −3.5 % ; 95 % CI , −13.6 % to 6.6 % ) or Arm 4 ( difference , −7.1 % ; 95 % CI , −16.1 % to 1.9 % ) . Graft dysfunction ( estimated glomerular filtration rate < 40 mL/min/1.73 m2 ) was the main determinant of composite-endpoint efficacy failure across all arms . Conclusions In patients representative of the European kidney 
    Output:
    
For induction therapy , no treatment appeared more effective than another in reducing graft loss or mortality .
Compared with placebo/no induction , rATG and BAS appeared more effective in reducing biopsy-proven acute rejection ( BPAR ) and BAS appeared more effective at improving GRF .
For maintenance therapy , no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss .
BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality .
MMF + CSA ( ciclosporin ) , TAC + MMF , SRL + TAC , TAC + AZA ( azathioprine ) and EVL + CSA appeared more effective  than CSA + AZA and EVL + MPS at reducing BPAR .
SRL + AZA , TAC + AZA , TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA .
In the base-case deterministic and probabilistic analyses , BAS , MMF and TAC were predicted to be cost-effective at £ 20,000 and £ 30,000 per quality -adjusted life-year ( QALY ) .
Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £ 20,000 - 30,000 per QALY .