***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    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 We performed a prospect i ve r and omized trial comparing sirolimus/mycophenolate mofetil (MMF)/prednisone to cyclosporine/MMF/prednisone and selected induction therapy with basiliximab .  Twenty patients received sirolimus ( 10 mg loading dose followed by 3 mg/m body surface area/day , keeping 24-hr trough levels at 10 - 15 ng/mL for six months and 5 - 10 ng/mL thereafter . Twenty-one patients began cyclosporine ( 4 to 8 mg/kg/day , keeping 12-hour trough levels at 150 - 300 ng/mL for 6 months and 100 - 200 ng/mL afterwards ) . Mean follow up was 15.8 months . One-year patient and graft survival was similar in both groups ( > 90 % ) . Acute rejection rate was 16.6 % in the sirolimus group and 5.2 % in the cyclosporine group ( P = NS ) . There were no differences in mean serum creatinine between groups . No patients who received basiliximab and had sirolimus target levels suffered acute rejection at one year . The sirolimus group had significantly higher cholesterol and triglycerides . A calcineurin inhibitor-free regimen using sirolimus produces comparable one-year transplant outcomes in living related kidney transplants compared to a calcineurin inhibitor regimen 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 The incidence of cardiovascular disease ( CVD ) is very high in patients with chronic kidney ( CKD ) disease and in kidney transplant recipients . Indeed , available evidence for these patients suggests that the 10‐year cumulative risk of coronary heart disease is at least 20 % , or roughly equivalent to the risk seen in patients with previous CVD . Recently , the National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative ( K/DOQI ) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD , including transplant patients . It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD , but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population . In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients . Evidence from the general population indicates that treatment of dyslipidemias reduces CVD , and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias . Dyslipidemias are very common in CKD and in transplant patients . However , until recently there have been no adequately powered , r and omized , controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD . Since completion of the K/DOQI guidelines on dyslipidemia in CKD , the results of the Assessment of Lescol in Renal Transplantation ( ALERT ) Study have been presented and published . Based on information from r and omized trials conducted in the general population and the single study conducted in kidney transplant patients , these guidelines , which are a modified version of the K/DOQI dyslipidemia guidelines , were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients . These guidelines are divided into four sections . The first section ( Introduction ) provides the rationale for the guidelines , and describes the target population , scope , intended users , and methods . The second section presents guidelines on the assessment of dyslipidemias  ( guidelines 1–3 ) , while the third section offers guidelines for the treatment of dyslipidemias  ( guidelines 4–5 ) . The key guideline statements are supported mainly by data from studies in the general population , but there is an urgent need for additional studies in CKD and in transplant patients . Therefore , the last section outlines recommendations for research Background . Everolimus is a proliferation inhibitor design ed to target chronic rejection , including prevention of acute rejection . Everolimus blocks growth factor-mediated transduction signals , preventing organ rejection by a mechanism different than that of calcineurin inhibitors and of mycophenolate mofetil ( MMF ) . Methods . Everolimus ( 1.5 mg or 3 mg daily ) was compared with MMF ( 2 g daily ) in a r and omized , multicenter , multinational , 12-month double-blind , double-dummy and 2-year open-label , phase 3 trial in de novo renal allograft recipients ( n=588 ) who also received cyclosporine and corticosteroids as part of a triple immunosuppressive regimen .  Results . At 12 months , there were no statistically significant differences between doses of 1.5 and 3 mg/day everolimus and MMF ( 2 g/day ) in incidence of biopsy-proven acute rejection ( 23.2 % , 19.7 % , and 24.0 % , respectively ) , graft loss ( 4.6 % , 10.6 % , and 9.2 % ) , or death ( 5.2 % , 4.0 % , and 2.6 % ) , respectively . Everolimus 1.5 mg/day and MMF were generally equally well tolerated . Both were better tolerated than everolimus 3 mg/day . The incidence of cytomegalovirus infection was significantly lower in patients receiving either 1.5 or 3 mg/day everolimus than in those receiving MMF ( 5.2 % and 7.6 % vs. 19.4 % , respectively ) ( P=.001 ) . Conclusions . Everolimus is effective in preventing acute rejection and graft loss in de novo renal allograft recipients receiving a triple immunosuppressive regimen . Prevention of acute rejection , along with reduction in cytomegalovirus infection , addresses two factors known to contribute to chronic rejection in such patients Background . This 36-month , r and omized , parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil ( MMF ) in de novo renal-transplant recipients . Methods . Renal-allograft recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF , plus full-dose cyclosporine ( CsA ) and corticosteroids after r and omization . For at least their first year , patients received study medication according to a double-blinded , double-dummy design . Concerns over nephrotoxicity led to a protocol amendment to an open-label design with reduced CsA troughs . Results . Incidences of primary efficacy failure at 36 months ( biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) were everolimus 1.5 mg/day , 33.7 % ( 65/193 ) ; everolimus 3 mg/day , 34.0 % ( 66/194 ) ; and MMF , 31.1 % ( 61/196 ) ( P=0.810 ) . Antibody-treated acute rejection at 36 months was significantly lower with everolimus 1.5 mg ( 9.8 % ) than MMF ( 18.4 % , P=0.014 ) . Discontinuation for adverse events was more frequent with everolimus and hemolytic uremic syndrome , lymphoproliferative disease , and proteinuria , and higher serum creatinine occurred at increased frequency relative to the MMF arm . Creatinine levels in the everolimus arms were stable in follow-up : the mean rise in creatinine over the first 6 months of the open-label phase was 3 & mgr;mol/L or greater with everolimus and 7 & mgr;mol/L with MMF . However , serum creatinine levels were lower in the MMF group throughout . Death and graft loss were higher in the everolimus arms ( not significant ) . Conclusions . As part of triple-drug immunosuppression , everolimus ( 1.5 or 3 mg/day ) was as efficacious as MMF , although the side-effect profile featured increased adverse events . Nephrotoxicity/calcineurin – inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs Background . Progressive nephrotoxicity caused by calcineurin inhibitor drugs contributes to the long-term decline in renal function in kidney transplant patients . Methods . We conducted a r and omized , prospect i ve trial of calcineurin inhibitor drug avoidance in 61 adult primary kidney transplant recipients . Each patient received induction therapy with 20 mg basiliximab on days 0 and 4 , and maintenance therapy with mycophenolate mofetil 1 g two times per day and steroids .  Thirty-one patients received sirolimus , 5 mg daily after a 15-mg loading dose . Doses were then concentration-controlled to keep 24-hr trough levels at 10 to 12 ng/mL for 6 months and 5 to 10 ng/mL thereafter . Thirty patients began cyclosporine therapy at 6 to 8 mg/kg per day in divided doses and were then concentration-controlled to keep 12-hr troughs of 200 to 250 ng/mL. Results . Mean follow-up is 18.1 months ( range , 12–26 months ) 
    Output:
    
From the four trials that measured lipoproteins , it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol .