Blog
About

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

      Serum Levels of Advanced Glycosylation End Products in Diabetic Nephropathy

      , ,

      Nephron

      S. Karger AG

      Advanced glycosylation end products, Diabetic nephropathy, Renal biopsy

      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/Aims: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. Results: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 ± 0.73 mU/ml; 15–24%, 4.01 ± 0.71 mU/ml; 25% or more, 5.12 ± 0.64 mU/ml). Conclusions: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.

          Related collections

          Most cited references 2

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

          Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure.

          In diabetes and ageing, glucose-derived advanced glycosylation endproducts (AGEs) cross-link proteins and cause vascular tissue damage. Elimination of circulating low-molecular weight AGE-modified molecules (LMW-AGEs) by the kidney is impaired in diabetic patients with end-stage renal disease, a group subject to accelerated atherosclerosis. We determined the effectiveness of current renal replacement treatments on elimination of serum LMW-AGEs in diabetic and non-diabetic patients with end-stage renal disease. Although diabetic patients receiving high-flux haemodialysis achieved 33% lower steady-state serum LMW-AGE than did those in conventional haemodialysis (p < 0.005), LMW-AGE concentrations remained 3.5-6 fold above normal, whether high-flux dialysis, conventional haemodialysis, or chronic ambulatory peritoneal dialysis were used. High-flux haemodialysis markedly reduced AGE during each treatment session (47.9% in the diabetic, p < 0.001 and 60.6% in the non-diabetic group, p < 0.001) but concentrations returned to pre-treatment range within 3 hours. In contrast, normal LMW-AGE concentrations were maintained in patients with functioning renal transplants. We found that LMW-AGEs with an apparent molecular weight of 2000-6000 circulate and retain strong inherent chemical reactivity--when exposed to collagen in vitro, up to 77% attached covalently to form AGE-collagen, and the AGE-crosslink inhibitor aminoguanidine completely inhibited this reaction. The results suggest that LMW-AGEs comprise a set of chemically-reactive molecules that are refractory to removal by current dialysis treatments. Through covalent reattachment onto vascular matrix or serum components, LMW-AGEs may exacerbate vascular pathology associated with end-stage renal disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus.

            The biochemical mechanisms that cause the development and progression of diabetic nephropathy are unknown. Advanced glycation end products (AGEs) might play a role, as shown by increased levels of tissue-bound and circulating AGEs that correlate with the severity of diabetic nephropathy. The aim of the present study was to investigate if circulating AGEs predict the progression of morphological pathology in patients with diabetic nephropathy. We have developed an immunoassay to determine serum levels of AGEs. In a prospective clinical trial of young insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria, kidney biopsies were taken at baseline and after 24 to 36 months. The biopsies were analyzed for structural changes in the glomeruli by quantitative morphometry (electron microscopy). We have retrospectively analyzed serum AGEs. The mean serum level of AGEs at the start of the study was 18.7 U/mL (95% confidence interval [CI], 16.9 to 20.5). A positive correlation between serum AGE levels at the start of study and changes from baseline to follow-up study in basement membrane thickness (r = .56, P < .02) and matrix/glomerular volume fraction (r = .57, P < .02) was demonstrated. In a stepwise regression analysis with changes in the matrix/glomerular volume fraction as the dependent variable, serum AGE levels at the start of the study proved to be a significant independent variable (P < .02), whereas the mean hemoglobin A1c (HbA1c) or HbA1c at the start was not. This study shows that serum AGEs predict the progression of early morphological kidney damage during 2.5 years in patients with IDDM.
              Bookmark

              Author and article information

              Journal
              NEF
              Nephron
              10.1159/issn.1660-8151
              Nephron
              S. Karger AG
              1660-8151
              2235-3186
              2001
              2001
              05 September 2001
              : 89
              : 2
              : 228-230
              Affiliations
              1st Department of Internal Medicine, Nara Medical University, Kashihara, Japan
              Article
              46073 Nephron 2001;89:228–230
              10.1159/000046073
              11549908
              © 2001 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: 1, Tables: 1, References: 19, Pages: 3
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/46073
              Categories
              Short Communication

              Comments

              Comment on this article