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

• Published in: American journal of transplantation Vol. 16; no. 11; pp. 3255 - 3261
• Main Authors: Dugast, E., Soulillou, J.‐P., Foucher, Y., Papuchon, E., Guerif, P., Paul, C., Riochet, D., Chesneau, M., Cesbron, A., Renaudin, K., Dantal, J., Giral, M., Brouard, S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01-11-2016; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; alloantibody; Antibodies; biopsy; Calcineurin; Calcineurin Inhibitors - administration & dosage; chronic allograft nephropathy; clinical research/practice; clinical trial; Clinical trials; Double-Blind Method; Evidence-based medicine; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft rejection; Graft Rejection - drug therapy; Graft Rejection - etiology; Graft Survival - drug effects; Histocompatibility antigen HLA; Human health and pathology; Humans; Immunization; Immunology; immunosuppressant; immunosuppression/immune modulation; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - surgery; Kidney Function Tests; Kidney transplantation; Kidney Transplantation - adverse effects; kidney transplantation/nephrology; Kidney transplants; Life Sciences; Male; Middle Aged; Postoperative Complications - drug therapy; Prospective Studies; Renal function; Side effects; Tacrolimus; Tacrolimus - administration & dosage; Transplant Recipients; Transplantation; Transplants & implants; Treatment Failure; Weaning; Young Adult; clinical trial; chronic allograft nephropathy; immunosuppression/immune modulation; clinical research/practice; kidney transplantation/nephrology; alloantibody; biopsy; immunosuppressant
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.13946

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.
A prospective, randomized, multicenter, double‐blind, placebo‐controlled clinical study shows the failure of tacrolimus withdrawal in highly stable kidney transplant patients.