title: Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety.
abstract: BACKGROUND
  Corticosteroid therapy after renal transplantation is associated with many adverse effects. Newer immunosuppressive agents may allow for safe and effective reductions in dose or early steroid withdrawal.
  
  
  METHODS
  In this prospective, single-center clinical trial, 60 patients were randomized into 2 groups: control patients (n = 28), who received low doses of prednisone throughout, and study patients (n = 32), who were withdrawn from steroids 7 days posttransplant. Patients received a limited course of rabbit antilymphocyte globulin (rALG) induction therapy, tacrolimus (TAC), and mycophenolate mofetil (MMF). Patients were followed for clinical outcomes and renal function. Protocol biopsies were performed at 1, 6, and 12 months.
  
  
  RESULTS
  Clinical rejections occurred in 11% of controls and 13% of study patients. Renal function was well maintained and equivalent in both groups. In all, 111 protocol biopsies were performed without complications. Subclinical rejection was noted in only 2 protocol biopsies, and borderline changes were seen in 12 biopsies, all of which were distributed equally between both groups. Unsuspected acute TAC toxicity was seen in 8 biopsies. Protocol biopsies led to changes in therapy in 10% of patients. In both groups, serial protocol biopsies demonstrated increased allograft fibrosis over time, which was significant at 1 year in the steroid withdrawal group.
  
  
  CONCLUSIONS
  The immunosuppressive combination of rALG, TAC, and MMF prevents subclinical rejection and the need for high doses of steroids after transplantation. However, continual low-dose steroid therapy may aid in preventing chronic allograft fibrosis. Protocol biopsies help define the short-term and long-term risks of steroid withdrawal therapy.
authors.affiliation: Departments of Surgery, SUNY-University at Buffalo, Buffalo General Hospital, Buffalo, NY, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Laftavi
authors.forename: Rabie
authors.initials: R
authors.lastname: Stephan
authors.forename: Barbara
authors.initials: B
authors.lastname: Stefanick
authors.forename: Romesh
authors.initials: R
authors.lastname: Kohli
authors.forename: Fadi
authors.initials: F
authors.lastname: Dagher
authors.forename: Mary
authors.initials: M
authors.lastname: Applegate
authors.forename: John
authors.initials: J
authors.lastname: O'Keefe
authors.forename: Drew
authors.initials: D
authors.lastname: Pierce
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubino
authors.forename: Haley
authors.initials: H
authors.lastname: Guzowski
authors.forename: Nicolae
authors.initials: N
authors.lastname: Leca
authors.forename: Merril
authors.initials: M
authors.lastname: Dayton
authors.forename: Oleh
authors.initials: O
authors.lastname: Pankewycz
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D005355:Fibrosis; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011241:Prednisone