Eculizumab in secondary atypical haemolytic uraemic syndrome

Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so-called secon...

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Autores: Cavero, Teresa, Rabasco, Cristina, López, Antía, Román, Elena, Ávila, Ana, Sevillano, Ángel, Huerta, Ana, Rojas-Rivera, Jorge, Fuentes, Carolina, Blasco, Miquel, Jarque, Ana, García, Alba, Mendizabal, Santiago, Gavela, Eva, Macía, Manuel, Quintana, Luis F., Romera, Ana María, Borrego, Josefa, Arjona, Emi, Espinosa, Mario, Portolés Pérez, José María, Gracia Iguacel, Carolina Marta, González Parra, Emilio José, Aljama, Pedro, Morales, Enrique, Cao, Mercedes, Rodríguez de Córdoba, Santiago, Praga, Manuel
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/680548
Acceso en línea:http://hdl.handle.net/10486/680548
https://dx.doi.org/10.1093/ndt/gfw453
Access Level:acceso abierto
Palabra clave:Atypical haemolytic uraemic syndrome
Complement activation
Eculizumab
Thrombotic microangiopathies
Medicina
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spelling Eculizumab in secondary atypical haemolytic uraemic syndromeCavero, TeresaRabasco, CristinaLópez, AntíaRomán, ElenaÁvila, AnaSevillano, ÁngelHuerta, AnaRojas-Rivera, JorgeFuentes, CarolinaBlasco, MiquelJarque, AnaGarcía, AlbaMendizabal, SantiagoGavela, EvaMacía, ManuelQuintana, Luis F.Romera, Ana MaríaBorrego, JosefaArjona, EmiEspinosa, MarioPortolés Pérez, José MaríaGracia Iguacel, Carolina MartaGonzález Parra, Emilio JoséAljama, PedroMorales, EnriqueCao, MercedesRodríguez de Córdoba, SantiagoPraga, ManuelAtypical haemolytic uraemic syndromeComplement activationEculizumabThrombotic microangiopathiesMedicinaBackground. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing conditionWork in this report was funded by the Instituto de Salud Carlos III: REDinREN (RD 016/009 Feder Funds), the Fondo de Investigaciones Sanitarias (13/02502 and ICI14/00350), the Ministerio de Economia y Competitividad (SAF2015-66287R) and the Autonomous Region of Madrid (S2010/BMD-2316; Grupo de Investigación Complemento-CM). SRdeC is funded by the Seventh Framework Programme European Union Project EURenOmics (305608)Oxford University Press on behalf of ERA-EDTA.Departamento de MedicinaFacultad de MedicinaInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)20172017-02-20research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/680548https://dx.doi.org/10.1093/ndt/gfw453reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6805482026-06-23T12:46:27Z
dc.title.none.fl_str_mv Eculizumab in secondary atypical haemolytic uraemic syndrome
title Eculizumab in secondary atypical haemolytic uraemic syndrome
spellingShingle Eculizumab in secondary atypical haemolytic uraemic syndrome
Cavero, Teresa
Atypical haemolytic uraemic syndrome
Complement activation
Eculizumab
Thrombotic microangiopathies
Medicina
title_short Eculizumab in secondary atypical haemolytic uraemic syndrome
title_full Eculizumab in secondary atypical haemolytic uraemic syndrome
title_fullStr Eculizumab in secondary atypical haemolytic uraemic syndrome
title_full_unstemmed Eculizumab in secondary atypical haemolytic uraemic syndrome
title_sort Eculizumab in secondary atypical haemolytic uraemic syndrome
dc.creator.none.fl_str_mv Cavero, Teresa
Rabasco, Cristina
López, Antía
Román, Elena
Ávila, Ana
Sevillano, Ángel
Huerta, Ana
Rojas-Rivera, Jorge
Fuentes, Carolina
Blasco, Miquel
Jarque, Ana
García, Alba
Mendizabal, Santiago
Gavela, Eva
Macía, Manuel
Quintana, Luis F.
Romera, Ana María
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés Pérez, José María
Gracia Iguacel, Carolina Marta
González Parra, Emilio José
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
author Cavero, Teresa
author_facet Cavero, Teresa
Rabasco, Cristina
López, Antía
Román, Elena
Ávila, Ana
Sevillano, Ángel
Huerta, Ana
Rojas-Rivera, Jorge
Fuentes, Carolina
Blasco, Miquel
Jarque, Ana
García, Alba
Mendizabal, Santiago
Gavela, Eva
Macía, Manuel
Quintana, Luis F.
Romera, Ana María
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés Pérez, José María
Gracia Iguacel, Carolina Marta
González Parra, Emilio José
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
author_role author
author2 Rabasco, Cristina
López, Antía
Román, Elena
Ávila, Ana
Sevillano, Ángel
Huerta, Ana
Rojas-Rivera, Jorge
Fuentes, Carolina
Blasco, Miquel
Jarque, Ana
García, Alba
Mendizabal, Santiago
Gavela, Eva
Macía, Manuel
Quintana, Luis F.
Romera, Ana María
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés Pérez, José María
Gracia Iguacel, Carolina Marta
González Parra, Emilio José
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
dc.subject.none.fl_str_mv Atypical haemolytic uraemic syndrome
Complement activation
Eculizumab
Thrombotic microangiopathies
Medicina
topic Atypical haemolytic uraemic syndrome
Complement activation
Eculizumab
Thrombotic microangiopathies
Medicina
description Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-02-20
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/680548
https://dx.doi.org/10.1093/ndt/gfw453
url http://hdl.handle.net/10486/680548
https://dx.doi.org/10.1093/ndt/gfw453
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press on behalf of ERA-EDTA.
publisher.none.fl_str_mv Oxford University Press on behalf of ERA-EDTA.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
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