“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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924000147
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Summary: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.
ISSN:2468-0249