title: Glomerular C3d as a novel prognostic marker for renal vasculitis.
abstract: Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d-positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis.
authors.affiliation: Nephrology Department, Hospital Universitario Fundacion Alcorcón, Alcorcón 28922, Spain. Electronic address: jvillacorta@fhalcorcon.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Villacorta
authors.affiliation: Pathology Department, Hospital Virgen de la Salud, Toledo 45004, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Crespo
authors.affiliation: Nephrology Department, Hospital Virgen de la Salud, Toledo 45004, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Acevedo
authors.affiliation: Pathology Department, Hospital Universitario Fundacion Alcorcón, Alcorcón 28922, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guerrero
authors.affiliation: Pathology Department, Hospital Virgen de la Salud, Toledo 45004, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos-Martin
authors.affiliation: Nephrology Department, Hospital Virgen de la Salud, Toledo 45004, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: García-Díaz
authors.affiliation: Pathology Department, Hospital Virgen de la Salud, Toledo 45004, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.affiliation: Nephrology Department, Hospital Universitario Fundacion Alcorcón, Alcorcón 28922, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Fernandez-Juarez
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015933:Complement C3d / Q000032:analysis*; D015935:Complement C4b; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d
keywords: Complement; Crescent; Glomerulus; Kidney; Vasculitis