title: Eculizumab in Pediatric Dense Deposit Disease.
abstract: OBJECTIVE
  Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children.
  
  
  METHODS
  The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis.
  
  
  RESULTS
  In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P<0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m(2), P<0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation.
  
  
  CONCLUSIONS
  In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.
authors: Department of Pediatric Nephrology and m.oosterveld@amc.nl.
authors: Michiel J S
authors: MJ
authors: Oosterveld
authors: Department of Pediatric Nephrology and.
authors: Mark R
authors: MR
authors: Garrelfs
authors: Department of Pediatrics, Division of Pediatric Nephrology, University Hospital Bonn, Bonn, Germany;
authors: Bernd
authors: B
authors: Hoppe
authors: Department of Pathology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands;
authors: Sandrine
authors: S
authors: Florquin
authors: Department of Pathology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands;
authors: Joris J T H
authors: JJ
authors: Roelofs
authors: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
authors: L P
authors: LP
authors: van den Heuvel
authors: Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Kerstin
authors: K
authors: Amann
authors: Department of Pediatric Nephrology and.
authors: Jean-Claude
authors: JC
authors: Davin
authors: Department of Pediatric Nephrology and.
authors: Antonia H M
authors: AH
authors: Bouts
authors: Department of Pediatric Nephrology and.
authors: Pietrik J
authors: PJ
authors: Schriemer
authors: Department of Pediatric Nephrology and.
authors: Jaap W
authors: JW
authors: Groothoff
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003182:Complement C5 / Q000037:antagonists & inhibitors; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007962:Leukocytes; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000209:etiology; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D014556:Urine / Q000166:cytology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D051056:Complement Inactivating Agents; C481642:eculizumab; D003404:Creatinine
keywords: C3 glomerulopathy; C3 nephritic factor; complement; dense deposit disease; glomerulonephritis; membranoproliferative