“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy
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
Abstract
IntroductionPost-transplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3-14% of kidney transplants (KT), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first three 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.MethodsWe retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA.ResultsKidney biopsy was performed in 91.1% of patients and complement genetic study in 64.4%. 85.4% of kidney biopsies showed signs of TMA; genetic analysis revealed one pathogenetic variant, two variants of uncertain significance, one likely benign variant, 8 risk polymorphisms, 27 risk haplotypes.After two weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After six months, 28.8% of patients had a complete renal recovery while 44.4% had a partial recovery.ConclusionThis 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.