High incidence of rejection episodes and poor tolerance of sirolimus in a protocol with early steroid withdrawal and calcineurin inhibitor-free maintenance therapy in renal transplantation: experiences of a randomized prospective single-center study.
Burkhalter F, Oettl T, et al.Transplantation Proceedings 2012; 44(10):2961-2965.
Aims
To compare the safety and efficacy of an immunosuppressive regimen with early corticosteroid withdrawal and maintenance immunosuppressive therapy of tacrolimus, sirolimus and mycophenolate sodium (MPS) for 3 months followed by a calcinineurin free or low-dose calcineurin regimen.
Interventions
All patients underwent early steroid withdrawal at 4 days posttransplant and received tacrolimus, MPS and sirolimus. At 3 months posttransplant patients were randomised to reduced-dose tacrolimus (target trough level of 4-8 ng/mL) versus tacrolimus elimination plus an increased sirolimus dose (target trough level of 8–12 ng/mL). Protocol biopsies were scheduled at 3 and 6 months posttransplant.
Participants
75 adult kidney transplant recipients
Outcomes
The primary outcome was kidney function at 6 months (glomerular filtration rate by Modification of Diet in Renal Disease equation). Secondary endpoints were clinical and subclinical biopsy-proven rejections, patient and graft survival, laboratory parameters of drug toxicity and side effects.
Follow-up
12 months
CET Conclusions
In this small trial in which patients have been randomised at 3 months to a CNI free regimen compared to maintenance with low dose CNI, the striking finding was the high withdrawal rate due to adverse events from sirolimus. Thus although the primary objective was to assess renal function at 6 months, the withdrawal rate was too high to allow any significant evaluation. Once again sirolimus appears to be an unacceptable drug to use from the time of transplantation.
Data analysis
Per protocol analysis
Trial registration
Not reported