Journal article
Eculizumab and recurrent C3 glomerulonephritis
Pediatric nephrology (Berlin, West), Vol.28(10), pp.1975-1981
10/2013
DOI: 10.1007/s00467-013-2503-y
PMCID: PMC4428658
PMID: 23689905
Abstract
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.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.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.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.
Details
- Title: Subtitle
- Eculizumab and recurrent C3 glomerulonephritis
- Creators
- Sevgi Gurkan - Department of Pediatrics, Division of Pediatric Nephrology Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey 89 French St., Rm. 2209 New Brunswick NJ 08901 USABillie Fyfe - Department of Pathology UMDNJ-Robert Wood Johnson Medical School New Brunswick NJ USALynne Weiss - Department of Pediatrics, Division of Pediatric Nephrology UMDNJ-Robert Wood Johnson Medical School New Brunswick NJ USAXue Xiao - Department of Medicine, Division of Nephrology and Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine University of Iowa 200 Hawkins Dr., 21151-A Iowa City IA 52242-1078 USAYuzhou Zhang - Department of Medicine, Division of Nephrology and Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine University of Iowa 200 Hawkins Dr., 21151-A Iowa City IA 52242-1078 USARichard Smith - Department of Medicine, Division of Nephrology and Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine University of Iowa 200 Hawkins Dr., 21151-A Iowa City IA 52242-1078 USA
- Resource Type
- Journal article
- Publication Details
- Pediatric nephrology (Berlin, West), Vol.28(10), pp.1975-1981
- DOI
- 10.1007/s00467-013-2503-y
- PMID
- 23689905
- PMCID
- PMC4428658
- NLM abbreviation
- Pediatr Nephrol
- ISSN
- 0931-041X
- eISSN
- 1432-198X
- Publisher
- Springer Berlin Heidelberg; Berlin/Heidelberg
- Language
- English
- Date published
- 10/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006367202771
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