title: Results of a prospective randomized trial of sirolimus conversion in kidney transplant recipients on early corticosteroid withdrawal.
abstract: BACKGROUND
  The use of calcineurin inhibitors is associated with chronic nephrotoxicity and lower glomerular filtration rate (GFR). As a result, one strategy of transplant immunosuppression is calcineurin inhibitor elimination.
  
  
  METHODS
  The aim of this study was to determine the outcome of a prospective randomized trial of kidney transplant recipients receiving rapid corticosteroid withdrawal, tacrolimus and mycophenolate mofetil (MMF) for 1 month followed by randomization to switch to sirolimus-MMF or to stay on tacrolimus-MMF. The primary outcome was the difference in measured GFR at 1 year using intention-to-treat analysis.
  
  
  RESULTS
  Sixty patients were randomized to stay on tacrolimus-MMF and 62 to sirolimus-MMF. Actual graft survival (including death) at 2 years was 98.4% in the sirolimus group, 96.7% in the tacrolimus group. Sixty-three percentage of the patients in the sirolimus group withdrew during the 2-year period of the study compared with 18% of the tacrolimus group (P<0.0001), primarily related to rejection or medication side effects. Rejection during the first year occurred in 5% of the tacrolimus group and 13% of the sirolimus group (P=0.15). Measured GFR at 1 year (mean±SD) was 57.4±20.7 mL/min/1.73 m in the sirolimus group and 62.7±26.5 mL/min/1.73 m in the tacrolimus group (95% CI of difference -3.7-14.4).
  
  
  CONCLUSIONS
  We conclude that conversion from tacrolimus-MMF to sirolimus-MMF at 1 month posttransplant in kidney recipients on rapid steroid withdrawal is poorly tolerated and does not improve GFR at 1 year.
authors.affiliation: Department of Medicine, Mayo Clinic in Arizona, Phoenix, AZ 85054, USA. Heilman.raymond@mayo.edu
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Heilman
authors.forename: Kerrie
authors.initials: K
authors.lastname: Younan
authors.forename: Hani M
authors.initials: HM
authors.lastname: Wadei
authors.forename: Martin L
authors.initials: ML
authors.lastname: Mai
authors.forename: Kunam S
authors.initials: KS
authors.lastname: Reddy
authors.forename: Harini A
authors.initials: HA
authors.lastname: Chakkera
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gonwa
mesh_terms: D000305:Adrenal Cortex Hormones; D000328:Adult; D000368:Aged; D000075202:Contraindications; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus