title: Eculizumab and recurrent C3 glomerulonephritis.
abstract: BACKGROUND
  Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease.
  
  
  METHODS
  In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of dense deposit disease (DDD) and allograft recurrence of C3 glomerulonephritis (C3GN) was treated with eculizumab every other week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/day at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 and 12 months.
  
  
  RESULTS
  Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease.
  
  
  CONCLUSIONS
  Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of the alternative pathway remained, indicating eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. gurkanse@umdnj.edu
authors.forename: Sevgi
authors.initials: S
authors.lastname: Gurkan
authors.forename: Billie
authors.initials: B
authors.lastname: Fyfe
authors.forename: Lynne
authors.initials: L
authors.lastname: Weiss
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001706:Biopsy; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D004334:Drug Administration Schedule; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D018579:Patient Selection; D012008:Recurrence; D012086:Reoperation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C038245:C3 protein, human; D003176:Complement C3; D007155:Immunologic Factors; C481642:eculizumab