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.
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control patients (n = 28), who received low doses of prednisone throughout, and study patients (n = 32), who were withdrawn from steroids 7 days posttransplant.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.
Laftavi
Mark R
MR
Departments of Surgery, SUNY-University at Buffalo, Buffalo General Hospital, Buffalo, NY, USA.
Stephan
Rabie
R
Stefanick
Barbara
B
Kohli
Romesh
R
Dagher
Fadi
F
Applegate
Mary
M
O'Keefe
John
J
Pierce
Drew
D
Rubino
Andrea
A
Guzowski
Haley
H
Leca
Nicolae
N
Dayton
Merril
M
Pankewycz
Oleh
O
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
D005938:Glucocorticoids; D011241:Prednisone