***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: 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 BACKGROUND The economic impact of therapies has increasingly become part of the clinical decision-making process . Costs associated with kidney transplantation are substantial and economic evaluations are useful in identifying immunosuppressive regimens that yield optimal clinical and economic benefits . METHODS Utilisation of health care re sources during the first 6-months after renal transplantation was examined in 557 kidney transplant recipients participating in a European , multicentre , r and omised , parallel group study that compared the efficacy and safety of a tacrolimus-based regimen versus a cyclosporin-microemulsion-based regimen .  Cost-minimisation and cost-effectiveness analyses were conducted from an Italian hospital perspective , including direct medical costs only ( e.g. medication , hospitalisation ) . RESULTS The incidence of acute rejection was significantly lower in the tacrolimus group than in the cyclosporin microemulsion ( ME ) group ( 32.5 % versus 51.3 % ; p<0.001 ) . Patient and graft survival  were similar in both treatment groups . Renal transplant recipients receiving tacrolimus-based immunosuppression had lower utilisation of health care re sources and lower total costs per patient than cyclosporin-ME treated patients . When surviving patients with a rejection-free graft were analysed , tacrolimus therapy was cost-saving , since it was both more effective ( 18.8 % difference in the incidence of acute rejection ; 95%CI 10.7%-26.8 % ; p<0.001 ) and less costly than cyclosporin-ME based therapy ( cost difference euro9918 ) . The costs per patient with a functioning graft were euro2305 , the costs per surviving patient were euro1892 lower in tacrolimus treated patients . Sensitivity analyses using the key cost-drivers ( hospitalisation , study drug , and concomitant medication ) found the cost advantage of tacrolimus was maintained . CONCLUSION In the first 6 months after renal transplantation , tacrolimus-based therapy was less costly than cyclosporin-ME based therapy . When surviving patients with a rejection-free graft were considered , tacrolimus was the dominant therapy Lipoprotein patterns in renal transplant patients : a comparison between FK 506 and cyclosporine A patients The development of diabetes mellitus in the renal transplant population was first reported by Starzl in 1964 and was attributed to the use of steroids.1 Since then ,  posttransplant diabetes mellitus has been associated with the use of other immunosuppressive agents , such as cyclosporine ( CyA ) . Because FK 506 is also thought to be diabetogenic,2 We retrospectively looked at the incidence of new onset diabetes mellitus in patients treated primarily with either FK 506 or CyA in a r and omized trial of kidney transplantations done at the University of Pittsburgh from February 1990 to May 1991 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 FK 506 was compared with cyclosporin in a r and omised trial in good-risk cadaveric renal transplant recipients . The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10 - 20 ng/ml would prove to be practical . Thirty-one adult patients were r and omised to FK 506 and 16 to cyclosporin .  Both groups received an identical regimen of azathioprine and corticosteroids .  Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks . One graft in the cyclosporin group was lost due to renal vein thrombosis . During the 6-week study period , 19.4 % of patients on FK 506 and 31.3 % on cyclosporin experienced acute rejection . One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy . Infections were reported in 51.6 % of the FK 506 group compared with 37.5 % of the cyclosporin group . The spectrum of adverse events was similar in both groups . However , minor neurological disorders were more common in the FK 506 group ( 54.8 % versus 6.3 % ) whereas hypertension was less common ( 48.8 % versus 75.0 % ) . The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients CONTEXT Tacrolimus , microemulsion cyclosporine ( Neoral ) , and mycophenolate mofetil ( MMF ) at 2 and 3 grams daily have demonstrated superior immunosuppressive properties in several recent clinical trials involving solid-organ transplants . An effective immunosuppression may be maintained with lower doses of MMF administered with either tacrolimus or microemulsion cyclosporine . OBJECTIVE To compare tacrolimus plus " low-dose " MMF-based immunosuppressive regimen ( TMBIR ) with Neoral plus " low-dose " MMF-based immunosuppressive regimens ( NMBIR ) among kidney transplant recipients . DESIGN Prospect i ve , r and omized study . PATIENTS 53 consecutive adult recipients of kidney transplant . Both groups ( TMBIR and NMBIR ) were equally matched on demographic characteristics . INTERVENTIONS Participants were r and omized to receive orally either tacrolimus ( 0.08 mg/kg twice daily ) ( n = 27 ) or Neoral ( 4 mg/kg twice daily ) ( n = 26 ) . Both regimens were started before surgery and continued when allograft demonstrated no postoperative acute tubular necrosis . Both groups received similar " low-dose " MMF ( 500 mg twice daily ) and prednisone ( 2 mg/kg/day to taper off after 1 year ) . Switch from tacrolimus to Neoral or vice versa was allowed after refractory rejection or serious adverse events . MAIN OUTCOME MEASURE Acute rejection and patient and graft survival 1 year following kidney transplant . RESULTS One-year patient survival rates were 88.9 % for the TMBIR group and 100 % for the NMBIR group ; 1-year graft survival rates were 88.9 % for the TMBIR group and 96.1 % for the NMBIR group . No significant differences were found in the incidence of biopsy-confirmed acute rejection ( 14.8 % TMBIR vs 23 % NMBIR ) . Steroid-resistant rejections requiring cytolytic antibody therapy were higher in the NMBIR group ( 50 % vs 25 % ) . Three patients crossed over from NMBIR to TMBIR for refractory rejections and 1 patient crossed over from TMBIR to NMBIR for new onset seizure . Three episodes of cytomegalovirus infection were observed in the TMBIR group . Other adverse events were similar in both groups . CONCLUSIONS Both tacrolimus and microemulsion cyclosporine combined with " low-dose " MMF and corticosteroids provide effective immunosuppression and have similar adverse events in kidney transplant recipients BACKGROUND Our clinical trial was design ed to investigate the optimal combination of immunosuppressants for renal transplantation . METHODS A r and omized three-arm , parallel group , open label , prospect i ve study was performed at 15 North American centers to compare three immunosuppressive regimens : tacrolimus + azathioprine ( AZA ) versus cyclosporine ( Neoral ) + mycophenolate mofetil ( MMF ) versus tacrolimus + MMF .  All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen . Only patients with delayed graft function ( 32 % ) received antilymphocyte induction . A total of 223 patients were r and omized , transplanted , and followed for 
    Output:
    
We demonstrated no differences in infection or malignancy .
AUTHORS ' CONCLUSIONS Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation , but increases post-transplant diabetes , neurological and gastrointestinal side effects .