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托珠单抗治疗肾移植受者微血管炎症:一项回顾性研究。

Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study.

作者信息

Noble Johan, Comai Giorgia, Corredetti Valeria, Laamech Reda, Dard Celine, Jouve Thomas, Giovannini Diane, Le Gouellec Audrey, Wadnerkar Shivani, Cravedi Paolo, Apuzzo Della, Vetrano Daniele, Busutti Marco, Abenavoli Chiara, Malvezzi Paolo, Rostaing Lionel Pe, Lamanna Gaetano

机构信息

Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, France.

Univ. Grenoble Alpes, CNRS, Inserm, U 1209 CNRS UMR 5309, Team Epigenetis Immunity, Metabolism, Cell Signaling and Cancer, Institute for advanced Biosciences, Grenoble, France.

出版信息

Transpl Int. 2025 May 16;38:14502. doi: 10.3389/ti.2025.14502. eCollection 2025.

Abstract

Chronic-active antibody mediated rejection (caAMR) is the leading causes of long-term kidney graft failure. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has been suggested as a treatment, but data are conflicting. We retrospectively studied consecutive adult kidney transplant recipients with caAMR or microvascular inflammation (MVI) without Donor-Specific Antibodies (DSA) and without C4d deposition (MVI + DSA-C4d-), who received TCZ as first-line therapy in two European centers. Estimated glomerular filtration rate (eGFR) and DSA were assessed one-year before and after TCZ initiation. The study included 64 patients who received TCZ between July 2018 and September 2023. The eGFR trajectory significantly decreased after TCZ treatment (-1.2 ± 0.2 vs. 0.03 ± 0.2 mL/min/1.73 m/month pre- vs. post-TCZ, respectively; p = 0.001). The percentage of patients with DSA decreased from 63.9% to 38.9% (p < 0.001), and the average MFI decreased from 9,537 to 7,250 (p = 0.001). In multivariate analysis, younger age (OR = 0.95, p = 0.02), MVI + DSA-C4d- phenotype (OR = 5.2, p = 0.01), and lower chronic glomerulopathy score (OR = 4.5, p = 0.02) were associated with TCZ response (trajectory ≥0 after TCZ). Patient survival was 98.4%, and graft survival was 93.7% at one-year. First-line TCZ therapy for caAMR or MVI + DSA-C4d- is associated with an improvement of eGFR trajectories, reduced DSA numbers and MFI and histological inflammation in glomeruli. These data suggest a potential benefit of TCZ in these settings.

摘要

慢性活动性抗体介导的排斥反应(caAMR)是长期肾移植失败的主要原因。托珠单抗(TCZ),一种抗白细胞介素-6受体抗体,已被提议作为一种治疗方法,但数据存在冲突。我们对两个欧洲中心连续接受TCZ作为一线治疗的成年肾移植受者进行了回顾性研究,这些受者患有caAMR或微血管炎症(MVI),且无供者特异性抗体(DSA)和C4d沉积(MVI + DSA-C4d-)。在开始使用TCZ之前和之后一年评估估计肾小球滤过率(eGFR)和DSA。该研究纳入了2018年7月至2023年9月期间接受TCZ治疗的64例患者。TCZ治疗后eGFR轨迹显著下降(TCZ治疗前与治疗后分别为-1.2±0.2与0.03±0.2 mL/min/1.73 m²/月;p = 0.001)。DSA阳性患者的比例从63.9%降至38.9%(p < 0.001),平均荧光强度(MFI)从9537降至7250(p = 0.001)。在多变量分析中,年轻(OR = 0.95,p = 0.02)、MVI + DSA-C4d-表型(OR = 5.2,p = 0.01)和较低的慢性肾小球病评分(OR = 4.5,p = 0.02)与TCZ反应(TCZ治疗后轨迹≥0)相关。一年时患者生存率为98.4%,移植肾生存率为93.7%。caAMR或MVI + DSA-C4d-的一线TCZ治疗与eGFR轨迹改善、DSA数量和MFI降低以及肾小球组织学炎症减轻相关。这些数据表明TCZ在这些情况下可能有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f34/12124137/dc7698d28726/TI_ti-2025-14502_wc_abs.jpg

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