Planned randomized conversion from tacrolimus to sirolimus-based immunosuppressive regimen in de novo kidney transplant recipients.
Silva HT, Felipe CR, et al.American Journal of Transplantation 2013; 13(12): 3155-3163.
Aims
To investigate the outcomes of converting tacrolimus (TAC) to sirolimus (SRL) 3 months following kidney transplant.
Interventions
Patients were randomised 3 months after transplantation surgery either to be converted from TAC to SRL or to be maintained on TAC.
Participants
299 recipients of first kidney transplant from brain-dead deceased or living related non-HLA identical donors.
Outcomes
The primary outcome was estimated glomerular filtration rate (eGFR) at 24-months. The secondary outcomes included eGFR of the on-therapy population, survival free from first biopsy proven acute rejection (BCAR) episodes, incidence of all treated acute rejections, clinical rejection, incidence and severity of all BCAR, patient and graft survival, treatment discontinuation, vital signs, adverse events and laboratory analysis at 24 months.
Follow-up
24 months
CET Conclusions
This multicentre open-label study randomised eligible patients at 3 months after renal transplantation to continue tacrolimus or switch to sirolimus in combination with MPS and prednisolone. At 24 months, there was no difference in renal function (estimated GFR) in the intention-to-treat population, with a higher urinary protein-creatinine ratio and non-significant increase in biopsy-proven acute rejection in the sirolimus arm. Protocol biopsies at 24 months demonstrated no difference in chronic lesions. Whilst these results are interesting, and the study appears well conducted (bar the absence of blinding), it should be noted that this is a very low-risk population of first-transplant recipients with a predominance of living donor transplants and relatively low early tacrolimus exposure. The protocol also excluded recipients with a GFR of less then 40ml/min at 3 months, who arguably have the most to gain from a switch to sirolimus. Also of note is the very low rate of discontinuation of sirolimus compared to previous studies.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01802268