AUTHOR=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 

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

JOURNAL=Transplant International

VOLUME=Volume 38 - 2025

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14502

DOI=10.3389/ti.2025.14502

ISSN=1432-2277

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/1.73m²/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.