Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study
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 c...
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Frontiers Media S.A.
2025-05-01
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| author | Johan Noble Johan Noble Johan Noble Giorgia Comai Giorgia Comai Valeria Corredetti Reda Laamech Celine Dard Thomas Jouve Thomas Jouve Diane Giovannini Audrey Le Gouellec Shivani Wadnerkar Paolo Cravedi Della Apuzzo Della Apuzzo Daniele Vetrano Daniele Vetrano Marco Busutti Chiara Abenavoli Chiara Abenavoli Paolo Malvezzi Lionel PE Rostaing Lionel PE Rostaing Gaetano Lamanna Gaetano Lamanna |
| author_facet | Johan Noble Johan Noble Johan Noble Giorgia Comai Giorgia Comai Valeria Corredetti Reda Laamech Celine Dard Thomas Jouve Thomas Jouve Diane Giovannini Audrey Le Gouellec Shivani Wadnerkar Paolo Cravedi Della Apuzzo Della Apuzzo Daniele Vetrano Daniele Vetrano Marco Busutti Chiara Abenavoli Chiara Abenavoli Paolo Malvezzi Lionel PE Rostaing Lionel PE Rostaing Gaetano Lamanna Gaetano Lamanna |
| author_sort | Johan Noble |
| collection | DOAJ |
| description | 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 m2/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. |
| format | Article |
| id | doaj-art-419c88f757f34e61908ec3f7b979b22d |
| institution | Kabale University |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-419c88f757f34e61908ec3f7b979b22d2025-08-20T03:49:37ZengFrontiers Media S.A.Transplant International1432-22772025-05-013810.3389/ti.2025.1450214502Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective StudyJohan Noble0Johan Noble1Johan Noble2Giorgia Comai3Giorgia Comai4Valeria Corredetti5Reda Laamech6Celine Dard7Thomas Jouve8Thomas Jouve9Diane Giovannini10Audrey Le Gouellec11Shivani Wadnerkar12Paolo Cravedi13Della Apuzzo14Della Apuzzo15Daniele Vetrano16Daniele Vetrano17Marco Busutti18Chiara Abenavoli19Chiara Abenavoli20Paolo Malvezzi21Lionel PE Rostaing22Lionel PE Rostaing23Gaetano Lamanna24Gaetano Lamanna25Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, FranceUniv. Grenoble Alpes, CNRS, Inserm, U 1209 CNRS UMR 5309, Team Epigenetis Immunity, Metabolism, Cell Signaling and Cancer, Institute for advanced Biosciences, Grenoble, FrancePrecision Immunology Institute, Translational Transplant Research Center (TTRC), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, FranceÉtablissement Français du Sang Auvergne-Rhône-Alpes, HLA and immunogenetics Laboratory, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, FranceUniv. Grenoble Alpes, CNRS, Inserm, U 1209 CNRS UMR 5309, Team Epigenetis Immunity, Metabolism, Cell Signaling and Cancer, Institute for advanced Biosciences, Grenoble, FranceAnatomopathology Department, University hospital Grenoble, Grenoble, FranceUniversité Grenoble Alpes, CNRS, Grenoble INP, CHU Grenoble Alpes, TIMC-IMAG, Grenoble, FrancePrecision Immunology Institute, Translational Transplant Research Center (TTRC), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesPrecision Immunology Institute, Translational Transplant Research Center (TTRC), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, ItalyNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University hospital Grenoble, Grenoble, FranceUniv. Grenoble Alpes, CNRS, Inserm, U 1209 CNRS UMR 5309, Team Epigenetis Immunity, Metabolism, Cell Signaling and Cancer, Institute for advanced Biosciences, Grenoble, FranceNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, ItalyChronic-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 m2/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.https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14502/fullkidney transplantationtocilizumabmicrovascular inflammationdonor-specific antibodychronic-active antibody-mediated rejection |
| spellingShingle | Johan Noble Johan Noble Johan Noble Giorgia Comai Giorgia Comai Valeria Corredetti Reda Laamech Celine Dard Thomas Jouve Thomas Jouve Diane Giovannini Audrey Le Gouellec Shivani Wadnerkar Paolo Cravedi Della Apuzzo Della Apuzzo Daniele Vetrano Daniele Vetrano Marco Busutti Chiara Abenavoli Chiara Abenavoli Paolo Malvezzi Lionel PE Rostaing Lionel PE Rostaing Gaetano Lamanna Gaetano Lamanna Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study Transplant International kidney transplantation tocilizumab microvascular inflammation donor-specific antibody chronic-active antibody-mediated rejection |
| title | Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study |
| title_full | Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study |
| title_fullStr | Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study |
| title_full_unstemmed | Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study |
| title_short | Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study |
| title_sort | tocilizumab based treatment of microvascular inflammation in kidney transplant recipients a retrospective study |
| topic | kidney transplantation tocilizumab microvascular inflammation donor-specific antibody chronic-active antibody-mediated rejection |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14502/full |
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