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在采用避免使用类固醇方案的贝拉西普转换肾移植受者中具有相似疗效。

Similar Efficacy in Belatacept-Converted Kidney Transplant Recipients With Steroid-Avoiding Regimen.

作者信息

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

机构信息

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.

出版信息

Kidney Int Rep. 2024 Dec 20;10(3):803-815. doi: 10.1016/j.ekir.2024.12.019. eCollection 2025 Mar.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

引言

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。

方法

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。

结果

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)。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b9a/11993219/fa5dacb75d7d/ga1.jpg

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