Journal Article

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

Couzi, Lionel, Leon, Juliette, Anglicheau, Dany, Herr, Florence, Durrbach, Antoine, Del Bello, Arnaud, Bertrand, Dominique, Ville, Simon, Grimbert, Philippe, Rostaing, Lionel, Kamar, Nassim, Noble, Johan, Le Meur, Yannick, Blancho, Gilles, Moulin, Bruno

2025

Overview

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 m 2 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.

• Publisher: Frontiers Media SA,Frontiers Media,Frontiers Media S.A
• Subject: Abatacept - therapeutic use / belatacept / Calcineurin inhibitors / Calcineurin Inhibitors - therapeutic use / Conversion / Desensitization / Diabetes / donor-specific antibodies / Effectiveness / eGFR / Epidermal growth factor receptors / Graft rejection / Graft Rejection - prevention & control / Graft Survival - drug effects / Health Archive / Hemodialysis / Humans / Immunosuppression / Immunosuppressive agents / Immunosuppressive Agents - therapeutic use / Inhibitors / Kidney transplantation / Kidney Transplantation - methods / Kidney transplants / Life Sciences / Lymphocytes / opportunistic infections / Patients / Rejection / Renal function / Steroids / Survival / TOR protein