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      Serum Levels of Antibodies Against Oxidised LDL in Kidney Graft Recipients

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          Abstract

          Background/Aims: Lipid abnormalities present in the post-transplant period may contribute to the development and progression of complications leading to graft and patient loss. In the present study serum levels of antibodies against oxidised LDL (Ab-oxLDL) in kidney graft recipients were investigated along with their possible relation to the development of complications in the post-transplant period, and to the outcome of kidney transplantation. Methods: Serum levels of Ab-oxLDL and lipid pattern were evaluated in 92 kidney graft recipients before and at 3, 6, 12, and 24 months after kidney transplantation, as well as in 90 healthy blood donors (control group). Results: Kidney graft recipients had higher frequency of low levels of Ab-oxLDL as compared with the control group. A decrease in Ab-oxLDL levels was observed at 6 months post-transplant. Patients with early graft loss due to acute rejection had lower pre-transplant Ab-oxLDL levels (p < 0.05) as compared to patients with graft survival >3 months. Conclusions: It is suggested that decreased Ab-oxLDL levels found in kidney graft recipients may reflect impaired response to the products of lipid oxidation or increased consumption of Ab-oxLDL, and are associated with graft loss due to acute rejection.

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          Autoantibody against oxidised LDL and progression of carotid atherosclerosis

          R Salonen, J.T. Salonen, H Korpela … (1992)
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            Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy.

            Kazi Islam, Dawn O’Byrne, Sridevi Devaraj … (2000)
            Atherosclerotic cardiovascular disease is the leading cause of death in patients with end stage renal disease (ESRD) who have undergone dialysis treatment. The oxidation of low density lipoprotein (LDL) appears to be a crucial step in the pathogenesis of atherosclerosis. The increased oxidative stress and attendant increased oxidizability of lipoproteins, such as LDL could contribute to the accelerated atherosclerosis in dialysis patients. Since alpha-tocopherol (AT) is the major antioxidant in LDL, the aim of the present study was to test the effectiveness of RRR-AT supplementation (800 I.U. per day) for 12 weeks on the susceptibility of LDL to oxidation. The study subjects comprised patients with chronic renal failure on hemodialysis (HD), peritoneal dialysis (PD), and age and sex matched controls (C). Plasma fatty acids, lipoproteins and AT levels were measured in these subjects before and after supplementation. Also, LDL AT and oxidizability was studied. LDL was isolated by ultracentrifugation at baseline and after 12 weeks of supplementation, and subjected to a 5-h time course of copper catalyzed oxidation. Oxidation was measured by the formation of conjugated dienes (CD) and lipid peroxides (LP). Supplementation with AT did not alter the plasma lipid or lipoprotein profile of these subjects. Plasma lipid-standardized AT and LDL AT concentrations were not different among the groups at baseline. AT supplementation significantly increased plasma lipid-standardized AT (C=150%, HD=149%, PD=217%, P<0.001) and LDL AT concentrations (C=94%, HD=94%, PD=135%, P<0.003). AT enrichment of LDL resulted in a significant prolongation in conjugated diene lag phase in all groups (C=34%, HD=21%, PD=54%, P<0.02). Lipid peroxide lag phase was also increased significantly in C (27%,) and PD (40%) groups after AT supplementation (P<0.01). There was a significant positive correlation between plasma lipid standardized AT and lag phase (r=0. 54, P=0.0003). Overall, AT decreased the susceptibility of LDL to oxidation in patients with chronic renal failure but the benefit appears to be greater in patients on PD. Therefore, AT supplementation may also provide a measure of protection against CAD in patients with chronic renal failure on dialysis therapy.
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              Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy.

              K. Islam, Trent McDonald, John S Grundy … (2001)
              Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure patients undergoing dialysis. In this study, we compared autoantibodies to oxidized low-density lipoprotein (OX-LDL), soluble cell adhesion molecules (CAMs), and the effect of both LDL and OX-LDL on monocyte endothelial cell adhesion in chronic renal failure patients on hemodialysis (HD, n = 16) and peritoneal dialysis (PD, n = 17) compared with matched healthy control subjects (C, n = 17). In addition, we studied the effect of supplementation with RRR-alpha-tocopherol (AT) 800 IU/d for 12 weeks on the above measures. LDL and OX-LDL induced adhesion of U937 cells to cultured endothelium, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin); autoantibodies to OX-LDL and markers of lipid peroxidation were determined before and after AT supplementation. Native LDL from PD patients induced greater monocyte-endothelial cell adhesion than LDL from C subjects (43.8% +/- 17.0% v25.3% +/- 17.7%, respectively, P = .0028). OX-LDL from chronic renal failure patients on both PD and HD stimulated greater adhesion than OX-LDL from the C subjects (68.0% +/- 18.5% and 57.6% +/- 15.1% v 40.9% +/- 17.3%, respectively, P < .01); OX-LDL from PD patients induced greater adhesion than that from HD patients (P < .01). Plasma methylglyoxal levels were significantly increased in both HD and PD groups, with higher levels in the HD group. Chronic renal failure patients on HD and PD also had higher levels of plasma sVCAM-1 and sE-selectin than C subjects (P < .01), indicating endothelial activation. Titers of autoantibodies to OX-LDL were not elevated in renal failure patients. Supplementation with AT 800 IU/d for 12 weeks, while resulting in significant enrichment with AT in LDL, did not have a significant effect on any of the parameters studied. This study makes the novel observation that the LDL of chronic renal failure patients on HD and PD appears to be potentially more atherogenic, since it induces greater monocyte-endothelial cell adhesion.
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                Author and article information

                Journal
                Journal ID (publisher-id): AJN
                Journal ID (nlm-ta): Am J Nephrol
                Journal ID (doi): 10.1159/issn.0250-8095
                Title: American Journal of Nephrology
                Publisher: S. Karger AG
                ISSN (Print): 0250-8095
                ISSN (Electronic): 1421-9670
                Publication date Subscription-year: 2002
                Publication date (Print): December 2002
                Publication date (Electronic): 07 October 2002
                Volume: 22
                Issue: 5-6
                Pages: 539-547
                Affiliations
                Departments of aMedical Sciences, and bPublic Health and Caring Sciences, Uppsala University, Uppsala, and cDepartment of Internal Medicine, Umeå University, Umeå, Sweden
                Article
                Publisher ID: 65293 Other ID: Am J Nephrol 2002;22:539–547
                DOI: 10.1159/000065293
                PubMed ID: 12381956
                SO-VID: 4faeb7d7-6e45-415b-b8e0-45d8f430d882
                Copyright © © 2002 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 : 07 December 2001
                Date accepted : 02 July 2002
                Page count
                Figures: 1, Tables: 5, References: 46, Pages: 9
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Lipid oxidation,Antibodies,Kidney transplantation
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Lipid oxidation, Antibodies, Kidney transplantation

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