Eculizumab in secondary atypical haemolytic uraemic syndrome
Por:
Cavero T, Rabasco C, Lopez A, Roman E, Avila A, Sevillano A, Huerta A, Rojas-Rivera J, Fuentes C, Blasco M, Jarque A, Garcia A, Mendizabal S, Gavela E, Macia M, Quintana LF, Maria Romera A, Borrego J, Arjona E, Espinosa M, Portoles J, Gracia-Iguacel C, Gonzalez-Parra E, Aljama P, Morales E, Cao M, Rodriguez de Cordoba S and Praga M
Publicada:
1 mar 2017
Resumen:
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
x 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 druginduced, 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.
Filiaciones:
Cavero T:
Department of Nephrology, Instituto de Investigacion Hospital 12 de Octubre (imas12), Madrid, Spain
Rabasco C:
Department of Nephrology, University Hospital Reina Sofia, Cordoba, Spain
Lopez A:
Department of Nephrology, University Hospital A Coruna, A Coruna, Spain
Roman E:
Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain
Avila A:
Department of Nephrology, University Hospital Dr Peset, Valencia, Spain
Sevillano A:
Department of Nephrology, Instituto de Investigacion Hospital 12 de Octubre (imas12), Madrid, Spain
Huerta A:
Department of Nephrology, University Hospital Puerta de Hierro, Madrid, Spain
Rojas-Rivera J:
Department of Nephrology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
Fuentes C:
Department of Hematology, University Hospital La Fe, Valencia, Spain
Blasco M:
Department of Nephrology, University Hospital Clinic, Barcelona, Spain
Jarque A:
Department of Nephrology, University Hospital Nuestra Senora de La Candelaria, Santa Cruz de Tenerife, Spain
:
Department of Nephrology, University Hospital A Coruna, A Coruna, Spain
Mendizabal S:
Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain
Gavela E:
Department of Nephrology, University Hospital Dr Peset, Valencia, Spain
Macia M:
Department of Nephrology, University Hospital Nuestra Senora de La Candelaria, Santa Cruz de Tenerife, Spain
Quintana LF:
Department of Nephrology, University Hospital Clinic, Barcelona, Spain
Maria Romera A:
Department of Nephrology, University Hospital de Ciudad Real, Ciudad Real, Spain
Borrego J:
Department of Nephrology, University Hospital de Jaen, Jaen, Spain
Arjona E:
Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid and Centro de Investigacion Biomedica en Red en Enfermedades Raras, Madrid, Spain
Espinosa M:
Department of Nephrology, University Hospital Reina Sofia, Cordoba, Spain
Portoles J:
Department of Nephrology, University Hospital Puerta de Hierro, Madrid, Spain
Gracia-Iguacel C:
Department of Nephrology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
Gonzalez-Parra E:
Department of Nephrology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
Aljama P:
Department of Nephrology, University Hospital Reina Sofia, Cordoba, Spain
Morales E:
Department of Nephrology, Instituto de Investigacion Hospital 12 de Octubre (imas12), Madrid, Spain
Cao M:
Department of Nephrology, University Hospital A Coruna, A Coruna, Spain
Rodriguez de Cordoba S:
Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid and Centro de Investigacion Biomedica en Red en Enfermedades Raras, Madrid, Spain
Praga M:
Department of Nephrology, Instituto de Investigacion Hospital 12 de Octubre (imas12), Madrid, Spain
Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain
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