Cargando…

Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic ure...

Descripción completa

Detalles Bibliográficos
Autores principales: Saleem, Maryam, Shaikh, Sana, Hu, Zheng, Pozzi, Nicola, Java, Anuja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204634/
https://www.ncbi.nlm.nih.gov/pubmed/35720299
http://dx.doi.org/10.3389/fimmu.2022.909503
_version_ 1784728969705160704
author Saleem, Maryam
Shaikh, Sana
Hu, Zheng
Pozzi, Nicola
Java, Anuja
author_facet Saleem, Maryam
Shaikh, Sana
Hu, Zheng
Pozzi, Nicola
Java, Anuja
author_sort Saleem, Maryam
collection PubMed
description Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary membranous nephropathy is an immune-mediated glomerular disease associated with circulating autoantibodies (directed against the M-type phospholipase A2 receptor (PLA2R) in 70% cases) while secondary membranous nephropathy is associated with infections, drugs, cancer, or other autoimmune diseases. Complement activation has also been proposed as a possible mechanism in the etiopathogenesis of primary membranous nephropathy; however, despite complement being a potentially common link, aHUS and primary membranous nephropathy have not been reported together. Herein we describe a case of aHUS due to a pathogenic mutation in complement factor I that developed after a kidney transplant in a patient with an underlying diagnosis of PLA2R antibody associated-membranous nephropathy. We highlight how a systematic and comprehensive analysis helped to define the etiology of aHUS, establish mechanism of disease, and facilitated timely treatment with eculizumab that led to recovery of his kidney function. Nonetheless, ongoing anti-complement therapy did not prevent recurrence of membranous nephropathy in the allograft. To our knowledge, this is the first report of a patient with primary membranous nephropathy and aHUS after a kidney transplant.
format Online
Article
Text
id pubmed-9204634
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92046342022-06-18 Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature Saleem, Maryam Shaikh, Sana Hu, Zheng Pozzi, Nicola Java, Anuja Front Immunol Immunology Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary membranous nephropathy is an immune-mediated glomerular disease associated with circulating autoantibodies (directed against the M-type phospholipase A2 receptor (PLA2R) in 70% cases) while secondary membranous nephropathy is associated with infections, drugs, cancer, or other autoimmune diseases. Complement activation has also been proposed as a possible mechanism in the etiopathogenesis of primary membranous nephropathy; however, despite complement being a potentially common link, aHUS and primary membranous nephropathy have not been reported together. Herein we describe a case of aHUS due to a pathogenic mutation in complement factor I that developed after a kidney transplant in a patient with an underlying diagnosis of PLA2R antibody associated-membranous nephropathy. We highlight how a systematic and comprehensive analysis helped to define the etiology of aHUS, establish mechanism of disease, and facilitated timely treatment with eculizumab that led to recovery of his kidney function. Nonetheless, ongoing anti-complement therapy did not prevent recurrence of membranous nephropathy in the allograft. To our knowledge, this is the first report of a patient with primary membranous nephropathy and aHUS after a kidney transplant. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9204634/ /pubmed/35720299 http://dx.doi.org/10.3389/fimmu.2022.909503 Text en Copyright © 2022 Saleem, Shaikh, Hu, Pozzi and Java https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Saleem, Maryam
Shaikh, Sana
Hu, Zheng
Pozzi, Nicola
Java, Anuja
Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title_full Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title_fullStr Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title_full_unstemmed Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title_short Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I in a Patient With Membranous Nephropathy: Case Report and Review of Literature
title_sort post-transplant thrombotic microangiopathy due to a pathogenic mutation in complement factor i in a patient with membranous nephropathy: case report and review of literature
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204634/
https://www.ncbi.nlm.nih.gov/pubmed/35720299
http://dx.doi.org/10.3389/fimmu.2022.909503
work_keys_str_mv AT saleemmaryam posttransplantthromboticmicroangiopathyduetoapathogenicmutationincomplementfactoriinapatientwithmembranousnephropathycasereportandreviewofliterature
AT shaikhsana posttransplantthromboticmicroangiopathyduetoapathogenicmutationincomplementfactoriinapatientwithmembranousnephropathycasereportandreviewofliterature
AT huzheng posttransplantthromboticmicroangiopathyduetoapathogenicmutationincomplementfactoriinapatientwithmembranousnephropathycasereportandreviewofliterature
AT pozzinicola posttransplantthromboticmicroangiopathyduetoapathogenicmutationincomplementfactoriinapatientwithmembranousnephropathycasereportandreviewofliterature
AT javaanuja posttransplantthromboticmicroangiopathyduetoapathogenicmutationincomplementfactoriinapatientwithmembranousnephropathycasereportandreviewofliterature