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      How Glomerular Extracapillary Proliferation Might Lead to Loss of Renal Function: Light Microscopic and Immunohistochemical Investigation

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          Abstract

          Although there has been extensive research into the mechanisms involved in glomerular crescent formation, it is not yet fully understood how this change may cause renal function impairment. The aim of this study is to identify morphologic changes which may be responsible for this phenomenon. Thirty-eight renal biopsies showing glomerulonephritis with extracapillary proliferation (20 vasculitis-related, 6 idiopathic, 9 due to immune-complex deposition and 3 superimposed on diabetic nephropathy) were considered, and 146 glomeruli in which both crescents and the urinary pole were found at the same time, were studied. The involvement of the urinary pole by cellular crescents was observed in 93.1 and 100% of the glomeruli with segmental or circumferential crescents, respectively. A tridimensional study, for the evaluation of the glomeruli as a whole, was performed on 8 biopsies by means of the step-section technique and disclosed the involvement of the urinary space and a close contact between crescent and tubular cells in all 54 investigated glomeruli. The reported features do not seem to be related to the type of cells which formed the crescent. Indeed, as shown by immunohistochemical study on 10 cases with anti-cytokeratin and anti-CD68 antisera, the crescent localization at the urinary pole had no correlation with the prevalence of epithelial or macrophagic cells. These findings suggest that crescents, due to epithelial proliferation or macrophage clustering, tend to localize at the urinary pole and thus come into close contact with cells of the proximal convoluted tubule: the formation of a sort of plug or a ‘glomerular stone’ could well explain the block in the urine flow and the consequent impairment of renal function in the acute phase of the disease, even in those cases where crescents are segmental.

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          Expression of the multifunctional extracellular matrix protein thrombospondin in crescentic glomerulonephritis.

          Thrombospondin is a multifunctional 450 kD glycoprotein which may be secreted into the extracellular matrix by a wide variety of cells. Occasional foci of immunoreactive thrombospondin have previously been demonstrated within normal human glomeruli. A specific polyclonal antibody directed against thrombospondin 1 was used to examine the distribution of this regulatory glycoprotein in renal biopsies from patients with a variety of renal diseases, including rapidly progressive glomerulonephritis associated with circulating antibodies to neutrophils, active or quiescent systemic lupus erythematosus, and membranous nephropathy, together with normal renal tissue. The results demonstrated the marked up-regulation of thrombospondin expression in acutely inflamed renal tissue with strongly positive, predominantly extracellular staining of glomerular crescents, although cytoplasmic staining of epithelial cells was also seen, indicating that these cells may contribute to thrombospondin accumulation at these sites. Occasional segmental mesangial staining was seen in cases of active lupus and rapidly progressive glomerulonephritis, while some focal interstitial staining around peritubular capillaries was seen in all renal tissue examined. These results suggest that thrombospondin may play an important role in the regulation of cellular recruitment, proliferation, and function in crescentic glomerulonephritis.
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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2002
            May 2002
            02 May 2002
            : 91
            : 1
            : 74-78
            Affiliations
            aDivisione di Nefrologia, Ospedali Riuniti di Bergamo; bDipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, e cDipartimento di Scienze Mediche, Università del Piemonte Orientale ‘Amedeo Avogadro’, Novara, Italia
            Article
            57607 Nephron 2002;91:74–78
            10.1159/000057607
            12021522
            © 2002 S. Karger AG, Basel

            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.

            Page count
            Figures: 5, Tables: 2, References: 18, Pages: 5
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/57607
            Categories
            Original Paper

            Cardiovascular Medicine, Nephrology

            Renal failure, Extracapillary glomerulonephritis, Crescents

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