Chavarot Nathalie, Cabezas Lara, Kaminski Hannah, Lazareth Helene, Try Mélanie, Leon Juliette, Scemla Anne, Jouve Thomas, Thervet Eric, Anglicheau Dany, Couzi Lionel, Sberro-Soussan Rebecca, Noble Johan
Nephrology and Kidney Transplantation Department, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Nephrology Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Kidney Int Rep. 2024 Dec 20;10(3):803-815. doi: 10.1016/j.ekir.2024.12.019. eCollection 2025 Mar.
Belatacept offers a valuable alternative to calcineurin inhibitors (CNIs) for reducing toxicity in kidney transplant recipients (KTRs). No study has evaluated the efficacy and safety of late-conversion belatacept with steroid avoidance in KTRs.
This retrospective multicentric study evaluated the efficacy and safety of a belatacept-based steroid-avoiding therapy, in comparison with concomitant steroid use. The study included KTRs from 4-French transplant centers who were converted to belatacept at least 6 months posttransplantation.
Overall, 512 KTRs were converted to belatacept in a median time of 38 (15.7-83.2) months after kidney transplantation (KT), including 199 patients without steroids after conversion (BelaS-). Median follow-up time was 78.9 (50.3-129.4) months. Compared with the 313 KTRs who had concomitant steroid use (BelaS+), BelaS- patients had a similar acute rejection (AR) rate (19 [6.1%] and 12 [6.0%] patients, = 0.126, including 13 [68.4%] and 5 [41.7%] T cell-mediated rejection in BelaS+ and BelaS- patients, respectively), and a similar graft survival (graft loss occurred in respectively 23 [7.3%] and 9 [4.5%] patients in BelaS+ and BelaS- groups [ = 0.198]). However, patient mortality was higher among BelaS+ patients (16.6% vs. 3%, < 0.001). Steroid use was an independent risk factor of mortality ( = 0.009) along with age ( = 0.0001) and diabetes ( = 0.001) at switch and the occurrence of severe infections with belatacept use ( = 0.0005). In addition, BelaS+ patients experienced a higher incidence of severe infections (cumulative incidence of 13.7 vs. 6.7 events/100-person-year), cytomegalovirus (CMV) disease ( < 0.001), infection by norovirus ( < 0.001), and hospitalization with COVID-19 ( < 0.001). BelaS+ patients were significantly more sensitized at conversion (donor-specific antibodies [DSA] in 21.8% vs. 6.6% in BelaS- patients, < 0.001). DSA incidence remained stable after conversion. BelaS+ patients developed significantly more DSA (14 [4.9%] vs. 2 [1.0%], < 0.001).
Avoiding steroids in KTRs who are late-converted to belatacept is associated with a similar efficacy along with lower mortality and reduced incidence of severe infections in selected low-sensitized patients.
贝拉西普为肾移植受者（KTRs）降低毒性提供了一种有价值的钙调神经磷酸酶抑制剂（CNIs）替代方案。尚无研究评估晚期转换为贝拉西普并避免使用类固醇在KTRs中的疗效和安全性。
这项回顾性多中心研究评估了与同时使用类固醇相比，基于贝拉西普的避免使用类固醇疗法的疗效和安全性。该研究纳入了来自4个法国移植中心的KTRs，他们在肾移植术后至少6个月转换为贝拉西普。
总体而言，512例KTRs在肾移植（KT）后中位时间38（15.7 - 83.2）个月转换为贝拉西普，其中199例转换后未使用类固醇（BelaS-）。中位随访时间为78.9（50.3 - 129.4）个月。与313例同时使用类固醇的KTRs（BelaS+）相比，BelaS-患者的急性排斥反应（AR）率相似（分别为19例[6.1%]和12例[6.0%]患者，P = 0.126，其中BelaS+和BelaS-患者中分别有13例[68.4%]和5例[41.7%]为T细胞介导的排斥反应），移植肾存活率相似（BelaS+组和BelaS-组分别有23例[7.3%]和9例[4.5%]患者发生移植肾丢失[P = 0.198]）。然而，BelaS+患者的死亡率更高（16.6%对3%，P < 0.001）。使用类固醇是死亡率的独立危险因素（P = 0.009），同时转换时的年龄（P = 0.0001）、糖尿病（P = 0.001）以及使用贝拉西普时发生严重感染（P = 0.0005）也是危险因素。此外，BelaS+患者发生严重感染的发生率更高（累积发生率为13.7对6.7事件/100人年）、巨细胞病毒（CMV）疾病（P < 0.001）、诺如病毒感染（P < 0.001）以及因COVID - 19住院（P < 0.001）。BelaS+患者在转换时致敏程度明显更高（供体特异性抗体[DSA]在BelaS+患者中为21.8%，在BelaS-患者中为6.6%，P < 0.001）。转换后DSA发生率保持稳定。BelaS+患者产生的DSA明显更多（14例[4.9%]对2例[1.0%]，P < 0.001）。
在晚期转换为贝拉西普的KTRs中避免使用类固醇与疗效相似，同时在选定的低致敏患者中死亡率更低且严重感染发生率降低相关。
