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Review
. 2025 May 20:38:14412.
doi: 10.3389/ti.2025.14412. eCollection 2025.

Belatacept in Kidney Transplantation: Reflecting on the Past, Shaping the Future

Johan Noble  1   2 , Juliette Leon  3 , Arnaud Del Bello  4 , Dany Anglicheau  3 , Gilles Blancho  5   6 , Simon Ville  5   6 , Lionel Couzi  7   8 , Philippe Grimbert  9   10 , Yannick Le Meur  11 , Bruno Moulin  12 , Nassim Kamar  4 , Lionel Rostaing  1 , Florence Herr #  13 , Antoine Durrbach #  13 , Dominique Bertrand #  14
Affiliations
Review

Belatacept in Kidney Transplantation: Reflecting on the Past, Shaping the Future

Johan Noble et al. Transpl Int. .

Abstract

Calcineurin inhibitors (CNIs) are a cornerstone of post-transplant immunosuppressive regimens. However, their use is associated with adverse effects, most notably chronic nephrotoxicity, which remains a leading cause of long-term allograft dysfunction. Belatacept, a selective costimulation blocker, offers a promising alternative to CNIs by aiming to reduce nephrotoxicity while maintaining efficacy in preventing acute rejection. While its use in de novo transplantation has been associated with improved graft and patient survival, it has also been linked to a higher incidence of acute rejection. Early post-transplantation conversion to belatacept has demonstrated significant improvements in renal function (eGFR gains ranging from +8.8 to +38.2 mL/min/1.73 m2 at 1 year post-conversion) but carries a higher risk of opportunistic infections. Late conversion protocols, typically initiated beyond 6 months post-transplantation, have shown sustained-although less pronounced-eGFR improvements and better long-term graft survival compared to CNI-based regimens. Additionally, belatacept appears to reduce the incidence of donor-specific antibodies. Future directions for the use of belatacept need further exploration, including its role in rescuing poor renal function, its combination with low-dose CNIs, mTOR inhibitors, or tocilizumab, and its application in desensitization protocols. By potentially striking a balance between efficacy and safety, belatacept may redefine the future landscape of transplant immunosuppression.

Keywords: belatacept; donor-specific antibodies; eGFR; kidney transplantation; opportunistic infections.

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Conflict of interest statement

Authors JN, JL, AD, DA, GB, SV, LC, PG, YL, BM, NK, LR, FH, AD, and DB declare consultancy fees from Bristol-Myers Squibb (BMS).

Figures

FIGURE 1
FIGURE 1
Belatacept current and future use in kidney transplantation. ATG, Antithymoglobulin; AR, Acute rejection; CMV, Cytomegalovirus; CNI, calcineurin inhibitors; DSA, Donor specific antibodies; eGFR, estimated glomerular filtration rate; mTORi, mammalian Target of Rapamycin inhibitors; RCTs, randomized controlled trials; TCZ, Tocilizumab.
See this image and copyright information in PMC

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