title: C3 Glomerulopathy.
abstract: Recent advances in our understanding of the disease pathology of membranoproliferative glomerulonephritis has resulted in its re-classification as complement C3 glomerulopathy (C3G) and immune complex-mediated glomerulonephritis (IC-GN). The new consensus is based on its underlying pathomechanism, with a key pathogenetic role for the complement alternative pathway (AP), rather than on histomorphological characteristics. In C3G, loss of AP regulation leads to predominant glomerular C3 deposition, which distinguishes C3G from IC-GN with predominant immunoglobulin G staining. Electron microscopy further subdivides C3G into C3 glomerulonephritis and dense deposit disease depending on the presence and distribution pattern of electron-dense deposits within the glomerular filter. Mutations or autoantibodies affecting the function of AP activators or regulators, in particular the decay of the C3 convertase (C3 nephritic factor), have been detected in up to 80 % of C3G patients. The natural outcome of C3G is heterogeneous, but 50 % of patients progress slowly and reach end-stage renal disease within 10-15 years. The new classification not only marks significant advancement in the pathogenic understanding of this rare disease, but also opens doors towards more specific treatment with the potential for improved outcomes.
authors.affiliation: Cell Biology Program of the Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.|Department of Paediatrics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.affiliation: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Thorner
authors.affiliation: Cell Biology Program of the Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. christoph.licht@sickkids.ca.|Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada. christoph.licht@sickkids.ca.|Department of Paediatrics, University of Toronto, Toronto, ON, Canada. christoph.licht@sickkids.ca.
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
mesh_terms: D000818:Animals; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016896:Treatment Outcome
chemical_list: C038245:C3 protein, human; D003176:Complement C3; D003178:Complement C3 Nephritic Factor
keywords: C3 Glomerulopathy; C3 Nephritic factor; Complement; Dense deposit disease; Eculizumab; Membranoproliferative glomerulonephritis