title: Treatment of C3 glomerulopathy with complement blockers.
abstract: C3 glomerulopathy (C3G) is a newly defined clinical entity comprising glomerular lesions with predominant C3 staining. Under this definition are now included membranoproliferative glomerulonephritis type II (dense deposit disease) and C3 glomerulonephritis. This group of glomerular diseases with a heterogeneous histological aspect shares a common pathogenesis, that is, a dysregulation of the alternative pathway of complement in the fluid phase leading to C3 deposition in the kidney. Recent advances have expanded our understanding of the underlying mechanisms, leading to the hypothesis that blocking the alternative complement pathway may be an effective treatment for C3Gs, as has been shown in other renal diseases driven by alternative pathway dysregulation, such as atypical hemolytic uremic syndrome. Results of 11 published cases of patients with different forms of C3G treated with eculizumab, an anti-C5 humanized monoclonal antibody, are encouraging. Given the complexity of disease pathogenesis in C3G, a patient-tailored approach including a comprehensive workup of complement abnormalities is necessary to evaluate the best treatment options. Clinical trials assessing effectiveness of different complement blockers on the background of the individual complement profile are needed.
authors.affiliation: Division of Nephrology and Dialysis, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.affiliation: Division of Nephrology and Dialysis, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003167:Complement Activation; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000276:immunology*; D003170:Complement Pathway, Alternative; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000235:genetics; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009154:Mutation; D010936:Plant Extracts / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000276:immunology; D029757:Tripterygium / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C509991:CR1 protein, human; D003176:Complement C3; D010936:Plant Extracts; D017463:Receptors, Complement 3b; C481642:eculizumab