Failure of Calcineurin Inhibitor (Tacrolimus) weaning randomized trial in long-term stable kidney transplant recipients.
Dugast E, Soulillou JP, et al.American Journal of Transplantation 2016 [record in progress].
Aims
To analyse the benefit–risk ratio of tacrolimus (TAC) weaning in highly selected patients.
Interventions
Participants were randomised to either the tacrolimus weaning (placebo NO TAC) arm, or the maintenance (TAC) arm.
Participants
10 kidney transplant recipients of a heart beating or living donor, aged 18-80 years, ≥4 years after transplantation with normal histology, stable graft function and no anti-HLA immunization.
Outcomes
Primary outcomes measured included improvement in renal function and glomerular filtration rate. Secondary measured outcomes were biopsy proven acute and chronic rejection, occurrence of or worsening interstitial fibrosis and tubular atrophy lesions (IFTA), de novo anti-HLA immunization, daily proteinuria, incidence of cancers, infections, cardiovascular and/or metabolic events, and assessment of the quality of life and graft loss.
Follow-up
1 year
CET Conclusions
This randomised controlled trial investigated a protocol with complete CNI withdrawal in a cohort of highly selected stable long-term renal transplant recipients. Patients had to be at least four years post-transplant, have stable function, no evidence of HLA antibodies and normal baseline histology. The trial was halted after recruitment of just 10 patients, as all 5 recruited to the tacrolimus-free arm had immunological events requiring CNI to be restarted. These results demonstrate that even in very stable patients many years after transplantation, complete CNI withdrawal is challenging. There are a few points of note regarding the study population here – all patients were receiving steroid-free immunosuppression, so those in the tacrolimus-free group ended up on MMF monotherapy. The inclusion criteria specified a minimum MPA AUC of 30 mg.h/L, but no data were provided as to the levels achieved in the five patients after tacrolimus withdrawal. This target level is quite low, particularly in the context of steroid-free immunosuppression, and resulted in doses as low as 1g/day in the monotherapy group. At the very least, CNI withdrawal will need to be combined with a higher level of baseline immunosuppression to stand a chance of success.
Data analysis
Per protocol analysis
Trial registration
Eudract - 2010-019574-33