Eculizumab in secondary atypical haemolytic uraemic syndrome.
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.



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.



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.



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.
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Teresa
T
Cavero
Department of Nephrology, University Hospital Reina Sofía, Córdoba, Spain.
Cristina
C
Rabasco
Department of Nephrology, University Hospital A Coruña, A Coruña, Spain.
Antía
A
López
Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain.
Elena
E
Román
Department of Nephrology, University Hospital Dr Peset, Valencia, Spain.
Ana
A
Ávila
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Ángel
Á
Sevillano
Department of Nephrology, University Hospital Puerta de Hierro, Madrid, Spain.
Ana
A
Huerta
Department of Nephrology, University Hospital Fundación Jiménez Díaz, Madrid, Spain.
Jorge
J
Rojas-Rivera
Department of Hematology, University Hospital La Fe, Valencia, Spain.
Carolina
C
Fuentes
Department of Nephrology, University Hospital Clinic, Barcelona, Spain.
Miquel
M
Blasco
Department of Nephrology, University Hospital Nuestra Señora de La Candelaria, Santa Cruz de Tenerife, Spain.
Ana
A
Jarque
Department of Nephrology, University Hospital A Coruña, A Coruña, Spain.
Alba
A
García
Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain.
Santiago
S
Mendizabal
Department of Nephrology, University Hospital Dr Peset, Valencia, Spain.
Eva
E
Gavela
Department of Nephrology, University Hospital Nuestra Señora de La Candelaria, Santa Cruz de Tenerife, Spain.
Manuel
M
Macía
Department of Nephrology, University Hospital Clinic, Barcelona, Spain.
Luis F
LF
Quintana
Department of Nephrology, University Hospital de Ciudad Real, Ciudad Real, Spain.
Ana
A
María Romera
Department of Nephrology, University Hospital de Jaén, Jaén, Spain.
Josefa
J
Borrego
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid and Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain.
Emi
E
Arjona
Department of Nephrology, University Hospital Reina Sofía, Córdoba, Spain.
Mario
M
Espinosa
Department of Nephrology, University Hospital Puerta de Hierro, Madrid, Spain.
José
J
Portolés
Department of Nephrology, University Hospital Fundación Jiménez Díaz, Madrid, Spain.
Carolina
C
Gracia-Iguacel
Department of Nephrology, University Hospital Fundación Jiménez Díaz, Madrid, Spain.
Emilio
E
González-Parra
Department of Nephrology, University Hospital Reina Sofía, Córdoba, Spain.
Pedro
P
Aljama
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Enrique
E
Morales
Department of Nephrology, University Hospital A Coruña, A Coruña, Spain.
Mercedes
M
Cao
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid and Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain.
Santiago
S
Rodríguez de Córdoba
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.|Department of Pediatric Nephrology, University Hospital La Fe, Valencia, Spain.
Manuel
M
Praga
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015267:Churg-Strauss Syndrome / Q000150:complications; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007677:Kidney Function Tests; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D010976:Platelet Count; D012008:Recurrence; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications; D057049:Thrombotic Microangiopathies / Q000188:drug therapy / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D007166:Immunosuppressive Agents; C481642:eculizumab; D003404:Creatinine
atypical haemolytic uraemic syndrome; complement activation; eculizumab; thrombotic microangiopathies