Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients

E. Dugast (1, 2, 3) , J.-P. Soulillou (1, 2, 3) , Y. Foucher (4) , E. Papuchon (1, 2, 5) , P. Guerif (1, 2, 5) , C. Paul (1, 2) , D. Riochet (6, 1, 2, 7) , M. Chesneau (1, 2) , A. Cesbron (8, 9) , K. Renaudin (1, 2, 3) , J. Dantal (1, 2) , Magali Giral (1, 2, 3, 8, 10) , Sophie Brouard (1, 2, 8, 10, 11)

1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 ITUN - Institut de transplantation urologie-néphrologie
3 Faculté de Médecine - Université de Nantes
4 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé
5 CIC biothérapies CBT 0503 [Nantes]
6 Département de pédiatrie [CHU Nantes]
7 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
8 LabEx TRANSPLANTEX [CHU de Nantes]
9 Etablissement Français du Sang [Nantes]
10 www.biodrim.eu - EU consortium BIO-DrIM [Berlin, Germany]
11 LabEX IGO Immunothérapie Grand Ouest

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a “low immunological risk of rejection” could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebocontrolled clinical study (Eudract: 2010-019574-33) to analyze the benefit–risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no antiHLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.

Mots clés: alloantibody; biopsy; chronic allograft nephropathy; clinical research/practice; clinical trial; immunosuppressant; immunosuppression/immune modulation; kidney transplantation/nephrology

Domaines: Médecine humaine et pathologie

E. Dugast, J.-P. Soulillou, Y. Foucher, E. Papuchon, P. Guerif, et al.. Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients. American Journal of Transplantation, 2016, 16 (11), pp.3255-3261. ⟨10.1111/ajt.13946⟩. ⟨inserm-02150143⟩