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

• DOI: 10.1111/ajt.13946
• Publication Date: 2016-07-01T14:31:12Z
• Authors: E. Dugast; J.-P. Soulillou; Y. Foucher; E. Papuchon; P. Guerif; C. Paul; D. Riochet; M. Chesneau; A. Cesbron; K. Renaudin; J. Dantal; M. Giral; S. Brouard
• Keywords: Adult; Graft Rejection; Male; immunosuppressant; Adolescent; Calcineurin Inhibitors; kidney transplantation/nephrology; immunosuppression/immune modulation; clinical research/practice; Kidney Function Tests; 03 medical and health sciences; Postoperative Complications; 0302 clinical medicine; Double-Blind Method; alloantibody; Humans; biopsy; Prospective Studies; Aged; Aged, 80 and over; Graft Survival; clinical trial; Middle Aged; Kidney Transplantation; 3. Good health; Kidney Failure, Chronic; Female; chronic allograft nephropathy; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Immunosuppressive Agents; Follow-Up Studies; Glomerular Filtration Rate

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 placebo-controlled 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 anti-HLA 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.