title: Atypical haemolytic uraemic syndrome treated with the complement inhibitor eculizumab: the experience of the Australian compassionate access cohort.
abstract: OBJECTIVE
  This study aimed to report the clinical characteristics and outcomes of Australian patients treated with eculizumab for atypical haemolytic uraemic syndrome (aHUS).
  
  
  METHODS
  A retrospective cohort study was undertaken of all patients in Australia treated with eculizumab provided in a compassionate access programme for a clinical diagnosis of aHUS using prospectively collected clinical data.
  
  
  RESULTS
  A total of 10 patients with a median age of 23.5 years (interquartile range (IQR) 24.83 years) received compassionate access eculizumab for aHUS in Australia. Eight patients were female, and three had a family history of aHUS. Three received eculizumab for an initial acute aHUS presentation, three for relapsing and refractory acute aHUS, two for de novo aHUS post-renal transplantation, and one each for aHUS recurrence post-transplantation and facilitation of transplantation with a history of aHUS. The median duration of eculizumab therapy has been 911.5 days (IQR 569 days) with a cumulative exposure of 9184 days. At baseline all patients had renal and extra-renal aHUS involvement, with up to three non-renal organs affected. All but one patient, who died from uncontrollable gastrointestinal aHUS manifestations, have continued. The nine continuing patients achieved remission of aHUS. Two of the four patients requiring renal replacement therapy (RRT) at eculizumab commencement subsequently ceased RRT. Clinical events occurring in this cohort while on eculizumab treatment included neutropenia (two), posterior reversible encephalopathy syndrome (one), cardiomyopathy (one), pulmonary embolus (one), antibody-mediated rejection resulting in renal graft failure (one), iron deficiency (one), gastrointestinal haemorrhage (one) and death (one).
  
  
  CONCLUSIONS
  Eculizumab has been an effective therapy for aHUS in this cohort, including when other therapies have failed.
authors.affiliation: Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.|Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Mallett
authors.affiliation: Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Hughes
authors.affiliation: Department of Clinical Haematology and BMT Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Szer
authors.affiliation: Department of Clinical Haematology and BMT Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Tuckfield
authors.affiliation: Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Van Eps
authors.affiliation: Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: S B
authors.initials: SB
authors.lastname: Cambell
authors.affiliation: Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Hawley
authors.affiliation: Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Burke
authors.affiliation: Department of Nephrology, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Kausman
authors.affiliation: Department of Nephrology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Hewitt
authors.affiliation: Department of Nephrology, Gold Coast Hospital, Gold Coast, Queensland, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Parnham
authors.affiliation: Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ford
authors.affiliation: Centre for Kidney Disease Research, Centre for Chronic Disease, CKD.QLD, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Isbel
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000150:complications* / Q000188:drug therapy*; D001315:Australia; D057176:Compassionate Use Trials; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; C481642:eculizumab
keywords: atypical haemolytic uraemic syndrome; eculizumab; thrombotic microangiopathy; transplantation