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.

“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy

Provenzano M.;
2024-01-01

Abstract

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.
2024
atypical hemolytic uremic syndrome
eculizumab
kidney transplant
thrombotic microangiopathy
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/366341
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