Minimization of Immunosuppressive Therapy After Renal Transplantation: Results of a Randomized Controlled Trial

Abstract

Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects.A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications.The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

New-Onset Diabetes after Kidney Transplantation

“…Whereas steroid withdrawal at 3 mo did not reduce the incidence of NODAT significantly, corticosteroid avoidance from the first day resulted in a significant reduction of NODAT (5.4 versus 0.4%; P ϭ 0.003) (27,28). Although it is known that the lower the corticosteroid dosages, the lower the long-term incidence of diabetes, corticosteroid withdrawal or dosage reduction must be balanced against the risk for acute rejection.…”

Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in De Novo Renal Transplantation: A Randomized Phase III Study

“…The primary endpoint comparison was performed by testing for noninferiority. Previous studies indicate that BPAR rate can be estimated at 20% (11)(12)(13)(14). Noninferiority was assessed using a prespecified 10% margin for the treatment difference in event rate.…”

Defining a Steroid Withdrawal Protocol in a newly established Kidney Transplantation Unit

“…In a group of patients steroids were withdrawn at 3 months. On review of the cases at 6 months, an increased AR rate and reduced cholesterol and low density lipoprotein (LDL) were noted in the steroid withdrawal group commencing from the period 3 up to 6 months post transplantation, refer to table 1 [7,15].…”

“…In order to withdraw steroids at an early stage after transplantation, a strong induction immunosuppression is necessary in order to avoid increased rates of AR. The justifi cation for early withdrawal or avoidance being that if steroid withdrawal is effected several weeks or months after transplantation the likelihood of provoking acute rejection would be increased, please read table 3 [15,26].…”