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      The Immunopathological Spectrum of Crescentic Glomerulonephritis: A Survey of 106 Patients in a Single Chinese Center

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          Abstract

          Background: Crescentic glomerulonephritis (CrGN) is a severe form of glomerular injury. We retrospectively analyzed data from Chinese patients with CrGN in our center to characterize the immunopathological spectrum of CrGN. Methods: A total of 106 consecutive patients with biopsy-proven CrGN were recruited. CrGN was classified into 3 types according to findings on immunofluorescence microscopy; type I was defined as a linear deposition of immunoglobulins along the glomerular basement membrane (GBM), type II as a glomerular deposition of immune-complex and type III as a pauci-immune deposition. Results: A total of 17/106 (16.0%) patients were classified as type I, 43/106 (40.6%) as type II and 46/106 (43.4%) as type III. Serum antineutrophil cytoplasmic antibodies (ANCA) could be detected in 1/17 (5.9%) patient with type I, 11/43 (25.6%) patients with type II and 29/46 (63.0%) patients with type III CrGN (p < 0.001). Serum anti-GBM antibodies could be detected in 14/17 (82.4%) patients with type I, 2/43 (4.7%) patients with type II and 3/46 (6.5%) patients with type III. In type II CrGN, ANCA-positive patients were older (p < 0.001), had more multi-system involvement (p < 0.001) and more fibrinoid necrosis in renal histopathology than ANCA-negative patients (p = 0.003). Conclusions: Pauci-immune CrGN might be the most common type of CrGN in Northern China. There was much heterogeneity within each type of CrGN.

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          Rapidly progressive crescentic glomerulonephritis.

          Charles Jennette (2003)
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            Clinical features and outcome of patients with both ANCA and anti-GBM antibodies.

            Jeremy Levy, Tarig Hammad, Anne Coulthart … (2004)
            Patients have been described who have both anti-neutrophil cytoplasm antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies. We have attempted to define the true prevalence of such "double positive" patients, and describe in detail their clinical features and outcome. We have reviewed all serologic assays performed between 1990 and 2000 in a single institution, and the case notes of patients having sera positive for both ANCA and anti-GBM antibodies. During this time 20,392 sera were initially tested for ANCA, and 4808 sera tested for anti-GBM antibodies. Five percent of all ANCA-positive serum samples were also positive for anti-GBM antibodies, and 32% of all anti-GBM positive samples had detectable ANCA. Of 27 patients with both antibodies, 82% had anti-myeloperoxidase specific P-ANCA. Pulmonary hemorrhage occurred in 44%. Renal biopsy showed extensive glomerular cellular crescents in most patients. Patient and renal survival rates were 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis-dependent at presentation, and none of these recovered renal function, despite immunosuppression with or without plasma exchange. Serologic evidence of double positivity for both ANCA and anti-GBM antibodies is common in patients with either antibody. In our study these patients have a poor prognosis when presenting with severe disease and initially behave more like anti-GBM disease than vasculitis. Recovery from severe renal failure is rare.
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              Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases.

              Mark Haas, Joseph A. Eustace (2004)
              Necrotizing and crescentic glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as "pauci-immune"; however, it is not unusual for renal biopsies in such cases to exhibit some immune complex deposition within glomeruli on immunofluorescence and/or electron microscopic study. The composition and intraglomerular localization of such deposits in ANCA-glomerulonephritis has not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested by some human and animal studies. Electron micrographs from 126 renal biopsies showing necrotizing/crescentic glomerulonephritis characterized by positive ANCA serology [C-ANCA, anti-proteinase 3 (anti-PR3), or anti-myeloperoxidase (MPO)] or necrotizing arteritis in the absence of known ANCA results were examined for the presence, quantity, and location of electron-dense deposits. The presence or absence of such deposits was correlated with histologic findings (fraction of glomeruli with crescents and segmental necrotizing lesions, mesangial and endocapillary hypercellularity), immunofluorescence findings, and clinical data, including serum creatinine and 24-hour urine protein levels at the time of biopsy. Sixty-eight (54%) of these biopsies showed glomerular immune complex deposits on electron microscopy; 87% of the latter also showed positive immunofluorescence findings for at least one immunoglobulin or complement component, although staining was relatively mild in most instances ( 2+). Hypercellularity within the glomerular tuft was seen in 50% of biopsies with deposits on electron microscopy but only 14% of those without deposits; in each group this was usually mild and mesangial. Notably, the presence of deposits on electron microscopy was associated with a higher median level of proteinuria (3.2 versus 1.3 g/24 hours, P < 0.0001) and a higher median percentage of glomeruli with crescents (62.5% versus 44.0%, P= 0.06). Immune complex deposits were found on electron microscopy in just over half of renal biopsies with crescentic glomerulonephritis associated with positive ANCA serology and/or necrotizing arteritis. Clinical correlations suggest that these immune complex deposits may somehow potentiate the effect of ANCA in producing glomerulonephritis.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2010
                Publication date (Print): August 2010
                Publication date (Electronic): 21 May 2010
                Volume: 116
                Issue: 1
                Pages: c65-c74
                Affiliations
                Renal Division, Department of Medicine, Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Peking University First Hospital, Peking University, Beijing, China
                Article
                Publisher ID: 314665 Other ID: Nephron Clin Pract 2010;116:c65–c74
                DOI: 10.1159/000314665
                PubMed ID: 20502041
                SO-VID: ad4d865b-567b-4c04-a745-a0c36ea621e9
                Copyright © © 2010 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 30 June 2009
                Date accepted : 29 December 2009
                Page count
                Figures: 1, Tables: 6, References: 37, Pages: 1
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Antineutrophil cytoplasmic antibodies,Anti-glomerular basement membrane,Crescentic glomerulonephritis,Immunofluorescence
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Antineutrophil cytoplasmic antibodies, Anti-glomerular basement membrane, Crescentic glomerulonephritis, Immunofluorescence

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