title: Eculizumab for treatment of rapidly progressive C3 glomerulopathy.
abstract: C3 glomerulopathy (C3G) is a prototypic complement-mediated kidney disease. Rapidly progressive forms of C3G usually respond poorly to conventional treatments. We report on the efficacy of the terminal complement inhibitor eculizumab in 3 adult patients with rapidly progressive C3G. In all 3 patients, serum creatinine levels had increased by >50% in the 2 months preceding initiation of eculizumab treatment despite the use of conventional immunosuppressive drugs and/or plasma exchanges in 2 of these individuals. Of note, 2 patients had long-standing nephrotic syndrome. Kidney biopsy performed prior to eculizumab treatment disclosed marked glomerular inflammatory changes and increased C5b-9 deposition in all patients. Eculizumab use was associated with significant improvement in kidney function, with estimated glomerular filtration rates of patients increasing 22 to 38 mL/min/1.73 m(2). Eculizumab use also was associated with remission of nephrotic syndrome in the 2 affected patients, an effect observed as early as one week after treatment initiation. Repeat kidney biopsy disclosed regression of glomerular inflammatory changes and decreases in glomerular staining for C5b-9 in all patients. These results warrant further assessment of eculizumab for treatment of rapidly progressive forms of C3G with markedly increased glomerular C5b-9 deposits.
authors.affiliation: Department of Nephrology, Hôpital Foch, Suresnes, France.
authors.forename: Moglie
authors.initials: M
authors.lastname: Le Quintrec
authors.affiliation: Department of Nephrology, CHU de Lille, Lille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lionet
authors.affiliation: Department of Pathology, CHU de Nantes, Nantes, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Kandel
authors.affiliation: Department of Nephrology, Clinique du Bois, Lille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdon
authors.affiliation: Department of Pathology, CHU de Lille, Lille, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Gnemmi
authors.affiliation: Department of Pathology, Hôpital Foch, Suresnes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Colombat
authors.affiliation: Department of Pathology, CHU de Poitiers, Poitiers, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Goujon
authors.affiliation: INSERM, UMR-S 872, and Department of Immunology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.affiliation: INSERM, UMR-S 1064, and Department of Nephrology and Immunology, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr.
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003176:Complement C3; C481642:eculizumab
keywords: C3 glomerulopathy (C3G); C5b-9 deposits; acute kidney injury (AKI); complement; complement alternative pathway; eculizumab; rapidly progressing glomerulonephritis