title: Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease.
abstract: BACKGROUND
  Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases.
  
  
  METHODS
  We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing.
  
  
  CONCLUSIONS
  The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. tran.cheryl2@mayo.edu.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Tran
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Carl H
authors.initials: CH
authors.lastname: Cramer
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sas
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Willrich
authors.affiliation: Department of Internal Medicine and Pediatrics, University of Iowa, Iowa City, IA, USA.|Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D007166:Immunosuppressive Agents; C481642:eculizumab
keywords: Alternative complement pathway; Dense deposit disease; Eculizumab; Hemodialysis; Soluble C5b-9