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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Causes and Consequences of Increased Arterial Stiffness in Chronic Kidney Disease Patients

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          Abstract

          Cardiovascular (CV) morbidity and mortality is greatly enhanced in patients with chronic kidney disease, compared to the non-renal population. One key element of this high CV burden appears to be arterial stiffness, as an expression of premature vascular aging. Increased arterial stiffness in renal patients may be a consequence of vascular calcification, chronic volume overload, inflammation, endothelial dysfunction, oxidative stress and several other factors. The authors review briefly the main pathophysiological mechanisms leading to reduced arterial compliance. Increased arterial stiffness has significant clinical consequences: isolated systolic hypertension, left ventricular hypertrophy (and failure), and reduced myocardial perfusion. Better knowledge of the mechanisms of arterial functional and morphologic alteration may help in developing more refined therapeutic strategies aimed to reduce the high CV burden in chronic kidney disease. The potential therapeutic interventions – mainly the use of certain antihypertensive drugs and reduction of vascular calcification – are finally discussed.

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          Clinical epidemiology of cardiovascular disease in chronic renal disease.

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            Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD.

            Patients with ESRD have a high circulating calcium (Ca) x phosphate (P) product and develop extensive vascular calcification that may contribute to their high cardiovascular morbidity. However, the cellular mechanisms underlying vascular calcification in this context are poorly understood. In an in vitro model, elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification independently and synergistically, a process that was potently inhibited by serum. Calcification was initiated by release from living VSMC of membrane-bound matrix vesicles (MV) and also by apoptotic bodies from dying cells. Vesicles released by VSMC after prolonged exposure to Ca and P contained preformed basic calcium phosphate and calcified extensively. However, vesicles released in the presence of serum did not contain basic calcium phosphate, co-purified with the mineralization inhibitor fetuin-A and calcified minimally. Importantly, MV released under normal physiologic conditions did not calcify, and VSMC were also able to inhibit the spontaneous precipitation of Ca and P in solution. The potent mineralization inhibitor matrix Gla protein was found to be present in MV, and pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. These data suggest that in the context of raised Ca and P, vascular calcification is a modifiable, cell-mediated process regulated by vesicle release. These vesicles contain mineralization inhibitors derived from VSMC and serum, and perturbation of the production or function of these inhibitors would lead to accelerated vascular calcification.
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              Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications.

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2007
                April 2007
                19 March 2007
                : 30
                : 2
                : 97-107
                Affiliations
                Dialysis and Renal Transplantation Center, Parhon University Hospital, Iasi, Romania
                Article
                100905 Kidney Blood Press Res 2007;30:97–107
                10.1159/000100905
                17374960
                7c487931-ebdb-466a-b3db-e696c9c8ffbc
                © 2007 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.

                History
                : 11 October 2006
                : 02 February 2007
                Page count
                Figures: 1, References: 105, Pages: 11
                Categories
                Review

                Cardiovascular Medicine,Nephrology
                End-stage renal disease,Arterial calcification,Arteriosclerosis,Arterial stiffness,Renal transplantation,Hemodialysis,Chronic kidney disease

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