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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 principales: 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., María Romera, Ana, Borrego, Josefa, Arjona, Emi, Espinosa, Mario, Portolés, José, Gracia-Iguacel, Carolina, González-Parra, Emilio, Aljama, Pedro, Morales, Enrique, Cao, Mercedes, Rodríguez de Córdoba, Santiago, Praga, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410989/
https://www.ncbi.nlm.nih.gov/pubmed/28339660
http://dx.doi.org/10.1093/ndt/gfw453
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author 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.
María Romera, Ana
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés, José
Gracia-Iguacel, Carolina
González-Parra, Emilio
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
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.
María Romera, Ana
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés, José
Gracia-Iguacel, Carolina
González-Parra, Emilio
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
author_sort Cavero, Teresa
collection PubMed
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 × 10(9)/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.
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spelling pubmed-54109892017-05-04 Eculizumab in secondary atypical haemolytic uraemic syndrome 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. María Romera, Ana Borrego, Josefa Arjona, Emi Espinosa, Mario Portolés, José Gracia-Iguacel, Carolina González-Parra, Emilio Aljama, Pedro Morales, Enrique Cao, Mercedes Rodríguez de Córdoba, Santiago Praga, Manuel Nephrol Dial Transplant Original Articles 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 × 10(9)/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. Oxford University Press 2017-03 2017-02-20 /pmc/articles/PMC5410989/ /pubmed/28339660 http://dx.doi.org/10.1093/ndt/gfw453 Text en © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
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.
María Romera, Ana
Borrego, Josefa
Arjona, Emi
Espinosa, Mario
Portolés, José
Gracia-Iguacel, Carolina
González-Parra, Emilio
Aljama, Pedro
Morales, Enrique
Cao, Mercedes
Rodríguez de Córdoba, Santiago
Praga, Manuel
Eculizumab in secondary atypical haemolytic uraemic syndrome
title 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_short Eculizumab in secondary atypical haemolytic uraemic syndrome
title_sort eculizumab in secondary atypical haemolytic uraemic syndrome
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410989/
https://www.ncbi.nlm.nih.gov/pubmed/28339660
http://dx.doi.org/10.1093/ndt/gfw453
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