Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial.
Bansal D, Yadav AK, et al.PLoS ONE [Electronic Resource] 2013; 8(10): e75591.
Aims
To investigate the effect on glomerular filtration rate (GFR) and Treg frequency by switching renal transplant patients from calcineurin inhibitor therapy (CNI) to sirolimus therapy (SRI).
Interventions
Participants were randomised to continue with CNI-therapy (tacrolimus or cyclosporine) or to receive SRI-therapy. All patients were administered with mycophenolate mofetil and prednisolone.
Participants
60 living donor kidney transplant recipients.
Outcomes
The primary endpoint was renal function assessed by serum-creatinine based GFR. Secondary endpoints included Treg population at 6 months, incidence of biopsy proven acute rejection, patient and graft survival, incidence of hyperlipidemia, new onset diabetes after transplantation, hypertension and infections.
Follow-up
6 months
CET Conclusions
This well-written manuscript details the results of a small open-label randomised controlled trial of long-term CNI versus switch to sirolimus from 2 months following renal transplantation. The population is a low-risk living-donor population on CNI, MMF and steroids, the majority of who received no antibody induction. The authors demonstrate a significant improvement in GFR at 180 days following switch in the sirolimus group compared to the CNI maintenance group, as well as an increased population of regulatory T cells. There are a few of aspects of this trial that are worth highlighting. The first is the relatively high withdrawal of consent rate from the trial (20%), which was higher in the sirolimus group (22.5 vs 13.8%). Despite this the authors report no difference in adverse event rates between the two cohorts. Secondly, despite the target trough levels for tacrolimus (the majority of patients) being 8-10ng/ml, the mean trough level in both groups was around 13 ng/ml at randomisation. Finally, the length of follow-up is very short; one would like to see longer-term results to confirm if the lower GFR is maintained in the sirolimus cohort.
Data analysis
Per protocol analysis
Trial registration
Clinical Trials Registry of India - CTRI/2011/091/000034