Blog
About

0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Analysis of Glomerular Anionic Charge Status in Children with IgA Nephropathy Using Confocal Laser Scanning Microscopy

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: The proteinuria resulting from IgA nephropathy is secondary to altered charge-selective and/or size-selective properties of the glomerular capillary walls. However, the functional changes occurring within the glomerular capillary network which lead to proteinuria are still poorly understood. In this study, we analyzed the participation of charged components in the glomerular capillary and their role with respect to proteinuria in childhood IgA nephropathy. Methods: We examined glomerular anionic charge in renal biopsy specimens with confocal laser scanning microscopy using FITC-conjugated poly- L-lysine as a cationic tracer. The renal specimens investigated were from 9 children with IgA nephropathy (IgAN(+)) associated with detectable proteinuria in a morning urine specimen, 8 children with IgA nephropathy (IgAN(–)) and 11 children with thin basement membrane disease (TBMD) with no detectable proteinuria. Results: The labeling intensity of glomerular fixed anionic sites from IgAN(+) was significantly lower than that of IgAN(–) and TBMD. Staining the serial sections following methylation treatment revealed that the labeling intensity for fixed anionic sites in TBMD was significantly higher than that of both IgAN(+) and IgAN(–). On the other hand, saponification treatment resulted in significantly more intensive fluorescence in TBMD and IgAN(–) than in IgAN(+). Furthermore, statistical analysis demonstrated a significant correlation between 24-hour protein excretion and the intensity of fixed anionic sites in all patients with IgA nephropathy at pH 7.0 and following staining with saponification treatment. Conclusions: These findings suggest that a reduction of glomerular anionic charge might be causally associated with the development of proteinuria in childhood IgA nephropathy. Furthermore, sulfate components such as heparan sulfate proteoglycan might be involved initially followed by carboxyl components such as sialoglycoproteins in the glomeruli of patients with IgA nephropathy contributing to the occurrence of proteinuria. We suggest that this method represents a straightforward approach to dissect the participation of charged components in the pathogenesis of childhood IgA nephropathy and their relationship to the development of glomerular proteinuria.

          Related collections

          Most cited references 4

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular basis of glomerular permselectivity.

          Recent discoveries in kidney research have given new insights into the molecular make-up of the glomerular filter and mechanisms of permselectivity. The identification of mutations in the genes for glomerular basement membrane type IV collagen has thus demonstrated the central role of the glomerular basement membrane as the structural skeleton of the glomerular capillary. Regional deterioration of this framework not only leads to proteinuria, but also to significant leakage of red blood cells into the urinary space. Tracer studies and the characterization of other glomerular basement membrane components, such as proteoglycans, have also emphasized the role of the glomerular basement membrane in the permselectivity process. However, more recent studies on nephrin, a key component of the slit diaphragm, as well as the podocyte and slit diaphragm-associated intracellular proteins, CD2-associated protein, podocin and alpha-actinin-4, have emphasized the role of the slit diaphragm as a central size-selective filtration barrier. These data have provided a completely new understanding of the mechanisms of proteinuria, both in inherited and acquired diseases. In this review, we present the recent progress made in the characterization of proteins that are important for glomerular permselectivity.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Minimal change nephropathy: An electrochemical disorder of the glomerular membrane

              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              Clinicopathologic Study on Prognostic Markers in IgA Nephropathy

              Background/Aim: Few prognostic markers have found general acceptance in IgA nephropathy (IgAN). The aim of the present study was to search for significant predictor(s) at the time of biopsy. Methods: Fifty-five patients with IgAN undergoing evaluation and treatment at our institution were examined regarding clinicopathologic features at the time of renal biopsy and, if possible, at follow-up. Factors predictive of outcome were evaluated. Renal histopathology was quantified using a glomerulosclerosis index (GSI), a tubulointerstitial index (TII), and a crescent index (CI). Results: The serum creatinine concentration (S-Cr) showed positive correlations with proteinuria and serum total cholesterol concentration, as well as with histopathologic findings. Heavy proteinuria (≧3.0 g/24 h) was associated with higher S-Cr and greater severity of pathologic abnormalities than with milder proteinuria. At follow-up, 6 patients progressed to chronic renal insufficiency, in whom the S-Cr increased by at least 50% to reach or exceed 1.5 mg/dl (132.6 µmol/l). By univariate analysis, elevated GSI, TII, and S-Cr, presence of nephrotic syndrome, elevated CI, and elevated total cholesterol were found to be negative predictors, in descending order of odds ratio. In multivariate analysis, however, only TII independently predicted unfavorable outcome. Conclusion: Renal biopsy in IgAN may be the most powerful predictor for renal outcome; an advanced tubulointerstitial lesion is unfavorable.
                Bookmark

                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2004
                March 2004
                17 November 2004
                : 96
                : 3
                : c96-c104
                Affiliations
                aDepartment of Pediatrics, Nara Medical University, Kashihara City, Nara, and bPediatric Clinic, Nara Prefectural Nara Hospital, Nara City, Nara, Japan
                Article
                76747 Nephron Clin Pract 2004;96:c96–c104
                10.1159/000076747
                15056992
                © 2004 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: 3, References: 23, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/76747
                Categories
                Original Paper

                Comments

                Comment on this article