title: Impact of early conversion from tacrolimus to sirolimus on chronic allograft changes in kidney recipients on rapid steroid withdrawal.
abstract: BACKGROUND
  Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy (IFTA).
  
  
  METHODS
  We conducted a prospective randomized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal. We compared the chronic changes (IFTA and sum of Banff chronic scores--Total Score) on protocol biopsies at 1 month, 1 year, and 2 years in all randomized patients. We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes.
  
  
  RESULTS
  We randomized 122 patients, 62 to sirolimus and 60 to tacrolimus. The 1-year biopsy was performed in 54 patients (90%) of the tacrolimus group and 56 patients (90%) of the sirolimus group. The proportion of biopsies with IFTA more than or equal to 2 and the Total Score more than 2 increased over the 2 years but were not different between the study groups at any time point. On the 1-year biopsy, there was more IFTA, and the fraction with Total Score more than 2 was higher in the tacrolimus group with previous rejection. In the cohort without rejection, there was a significant progression of the IFTA and Total Score between 1 and 2 years in both the sirolimus and tacrolimus groups.
  
  
  CONCLUSIONS
  Conversion from tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal does not decrease the progression of chronic changes on protocol biopsies during the first 2 years even in those patients without previous acute rejection.
authors: Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA. Heilman.raymond@mayo.edu
authors: Raymond L
authors: RL
authors: Heilman
authors: Cherise
authors: C
authors: Cortese
authors: Xochiquetzal J
authors: XJ
authors: Geiger
authors: Kerrie
authors: K
authors: Younan
authors: Hani M
authors: HM
authors: Wadei
authors: Martin L
authors: ML
authors: Mai
authors: Kunam S
authors: KS
authors: Reddy
authors: Thomas A
authors: TA
authors: Gonwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D001706:Biopsy; D000075202:Contraindications; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use*; D013256:Steroids; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D028761:Withholding Treatment
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D020123:Sirolimus; D016559:Tacrolimus