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

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,...

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Bibliographic Details
Published in:American journal of transplantation 2016-11, Vol.16 (11), p.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: Article
Language:English
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
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Description
Summary: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.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.13946