“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy
Introduction: Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months af...
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Elsevier
2024-04-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924000147 |
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| author | Federica Maritati Valeria Corradetti Claudia Bini Michele Provenzano Vania Cuna Marco Busutti Francesco Tondolo Fulvia Zappulo Gisella Vischini Francesca Iacovella Chiara Abenavoli Greta Borelli Marcello Demetri Benedetta Fabbrizio Giorgia Radi Matteo Ravaioli Caterina Mele Gaetano La Manna Giorgia Comai |
| author_facet | Federica Maritati Valeria Corradetti Claudia Bini Michele Provenzano Vania Cuna Marco Busutti Francesco Tondolo Fulvia Zappulo Gisella Vischini Francesca Iacovella Chiara Abenavoli Greta Borelli Marcello Demetri Benedetta Fabbrizio Giorgia Radi Matteo Ravaioli Caterina Mele Gaetano La Manna Giorgia Comai |
| author_sort | Federica Maritati |
| collection | DOAJ |
| description | Introduction: Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA. Methods: We retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA. Results: Kidney biopsy was performed in 91.1% of patients, and complement genetic study was performed in 64.4%. Of the kidney biopsies, 85.4% showed signs of TMA; genetic analysis revealed 1 pathogenetic variant, 2 variants of uncertain significance, 1 likely benign variant, 8 risk polymorphisms, and 27 risk haplotypes. After 2 weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After 6 months, 28.8% of patients had a complete renal recovery whereas 44.4% had a partial recovery. Conclusion: This is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function. |
| format | Article |
| id | doaj-art-de65637b257841daa41243a883582a7e |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-de65637b257841daa41243a883582a7e2025-08-20T03:20:19ZengElsevierKidney International Reports2468-02492024-04-019498299310.1016/j.ekir.2024.01.013“Eculizumab First” in the Management of Posttransplant Thrombotic MicroangiopathyFederica Maritati0Valeria Corradetti1Claudia Bini2Michele Provenzano3Vania Cuna4Marco Busutti5Francesco Tondolo6Fulvia Zappulo7Gisella Vischini8Francesca Iacovella9Chiara Abenavoli10Greta Borelli11Marcello Demetri12Benedetta Fabbrizio13Giorgia Radi14Matteo Ravaioli15Caterina Mele16Gaetano La Manna17Giorgia Comai18Nephrology, 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, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department 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, Italy; Department 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, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department 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, Italy; Department 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 and Dialysis Unit, Azienda USL della Romagna, Infermi Hospital, Rimini, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department 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, ItalyPathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyHepato-biliary Surgery and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy; Hepato-biliary Surgery and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Clinical Research Center for Rare Diseases Aldo e Cele Daccò Ranica, Bergamo, ItalyNephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy; Correspondence: Gaetano La Manna, Unità Operativa di Nefrologia, Dialisi, Trapianto, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 13, 40138 Bologna, Italy.Nephrology, Dialysis and Kidney Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, ItalyIntroduction: Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA. Methods: We retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA. Results: Kidney biopsy was performed in 91.1% of patients, and complement genetic study was performed in 64.4%. Of the kidney biopsies, 85.4% showed signs of TMA; genetic analysis revealed 1 pathogenetic variant, 2 variants of uncertain significance, 1 likely benign variant, 8 risk polymorphisms, and 27 risk haplotypes. After 2 weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After 6 months, 28.8% of patients had a complete renal recovery whereas 44.4% had a partial recovery. Conclusion: This is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.http://www.sciencedirect.com/science/article/pii/S2468024924000147thrombotic microangiopathyatypical hemolytic uremic syndromekidney transplanteculizumab |
| spellingShingle | Federica Maritati Valeria Corradetti Claudia Bini Michele Provenzano Vania Cuna Marco Busutti Francesco Tondolo Fulvia Zappulo Gisella Vischini Francesca Iacovella Chiara Abenavoli Greta Borelli Marcello Demetri Benedetta Fabbrizio Giorgia Radi Matteo Ravaioli Caterina Mele Gaetano La Manna Giorgia Comai “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy Kidney International Reports thrombotic microangiopathy atypical hemolytic uremic syndrome kidney transplant eculizumab |
| title | “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy |
| title_full | “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy |
| title_fullStr | “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy |
| title_full_unstemmed | “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy |
| title_short | “Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy |
| title_sort | eculizumab first in the management of posttransplant thrombotic microangiopathy |
| topic | thrombotic microangiopathy atypical hemolytic uremic syndrome kidney transplant eculizumab |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924000147 |
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