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Randomized Controlled Trial
. 2022 Nov 28:13:1021481.
doi: 10.3389/fimmu.2022.1021481. eCollection 2022.

Case Report: Long-term observations from the tacrolimus weaning randomized clinical trial depicts the challenging aspects for determination of low-immunological risk patients

Collaborators, Affiliations
Randomized Controlled Trial

Case Report: Long-term observations from the tacrolimus weaning randomized clinical trial depicts the challenging aspects for determination of low-immunological risk patients

Christophe Masset et al. Front Immunol. .

Abstract

Whilst calcineurin inhibitors (CNI) are the cornerstone of immunosuppressive maintenance therapy in kidney transplantation, several studies have investigated the safety of CNI withdrawal in order to avoid their numerous side effects. In this context, we performed several years ago a clinical randomized trial evaluating CNI weaning in stable kidney transplant recipients without anti-HLA immunization. The trial was interrupted prematurely due to a high number of de novo DSA (dnDSA) and biopsy proven acute rejection (BPAR) in patients who underwent tacrolimus weaning, resulting in treatment for rejection and resumption of tacrolimus. We report here the long-term outcomes of patients included in this clinical trial. Ten years after randomization, all patients are alive with a functional allograft. They all receive tacrolimus therapy except one with recurrent cutaneous neoplasia issues. Long-term eGFR was comparable between patients of the two randomized groups (46.4 ml/min vs 42.8 ml/min). All dnDSA that occurred during the study period became non-detectable and all rejections episodes were reversed. The retrospective assessment of HLA DQ single molecule epitope mismatching determined that a majority of patients who developed dnDSA after tacrolimus withdrawal would have been considered at high immunological risk. Minimization of immunosuppression remains a challenging objective, mainly because of the issues to properly select very low immunological risk patients. Valuable improvements have been made the last decade regarding evaluation of the allograft rejection notably through the determination of numerous at-risk biomarkers. However, even if the impact of such tools still need to be clarify in clinical routine, they may permit an improvement in patients' selection for immunosuppression minimization without increasing the risk of allograft rejection.

Trial registration: ClinicalTrials.gov NCT01292525.

Keywords: allograft rejection; calcineurin inhibitor withdrawal; case report; donor specific antibodies; kidney transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Long-term evolution of allograft function of patients included in the CNI weaning protocol. All patients with a decrease > 50% of eGFR at long-term were those with IgA glomerulonephritis recurrence. (B) Long-term evolution of proteinuria of patients included in the CNI weaning protocol. (C) Representation of DSA’s maximal MFI. 3/5 patients who underwent tacrolimus withdrawal presented an early occurrence of de novo DSA with a MFI > 2000, quickly reversed after specific treatment. 2 patients developed a de novo DSA long term after the study, independently of their inclusion group.

References

    1. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med (2004) 351:2715–29. doi: 10.1056/NEJMra033540 - DOI - PubMed
    1. Coemans M, Süsal C, Döhler B, Anglicheau D, Giral M, Bestard O, et al. . Analyses of the short- and long-term graft survival after kidney transplantation in Europe between 1986 and 2015. Kidney Int (2018) 94:964–73. doi: 10.1016/j.kint.2018.05.018 - DOI - PubMed
    1. Cantarovich D, Rostaing L, Kamar N, Ducloux D, Saint-Hillier Y, Mourad G, et al. . Early corticosteroid avoidance in kidney transplant recipients receiving ATG-f induction: 5-year actual results of a prospective and randomized study. Am J Transpl (2014) 14:2556–64. doi: 10.1111/ajt.12866 - DOI - PubMed
    1. Thomusch O, Wiesener M, Opgenoorth M, Pascher A, Woitas RP, Witzke O, et al. . Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet Lond Engl (2016) 388:3006–16. doi: 10.1016/S0140-6736(16)32187-0 - DOI - PubMed
    1. Kampf C, Lau T, Olsson R, Leung PS, Carlsson P-O. Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts. Diabetologia (2005) 48:1159–67. doi: 10.1007/s00125-005-1761-z - DOI - PubMed

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