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      Cell-Crystal Interactions and Kidney Stone Formation

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          Abstract

          Background: Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. How these nascent crystals are retained in the nephron to form calculi in certain individuals is not known. Methods: The results of experiments conducted in this and other laboratories that employ cell culture model systems to explore renal epithelial cell-urinary crystal interactions are described. Results: COM crystals rapidly adhere to anionic sites on the surface of cultured renal epithelial cells, but this process can be inhibited, if specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, or citrate are available to coat the crystalline surface. Therefore, competition for the crystal surface between soluble anions in tubular fluid and anions on the apical cell surface could determine whether or not a crystal binds to the cell. A similar paradigm describes adhesion of calcium phosphate (hydroxyapatite) crystals, also a common constituent of human stones. Once bound, COM and hydroxyapatite crystals are quickly internalized by renal cells; reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation may then ensue. Each of these cellular events appears to be regulated by a different set of extracellular factors. Over several weeks in culture, renal cells (BSC-1 line) dissolve internalized crystals, although once a cell binds a crystal, additional crystals are more likely to bind, possibly forming a positive feedback loop that results in kidney stone formation. Conclusions: Increased knowledge about the cell-crystal interaction, including identification of molecules in tubular fluid and on the cell surface that modulate the process, and understanding its mechanism of action appear critical for explaining the pathogenesis of nephrolithiasis.

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          Most cited references 6

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          Apoptosis. Phagocytic docking without shocking.

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            Oxalate-induced initiation of DNA synthesis in LLC-PK1 cells, a line of renal epithelial cells.

            These studies examined the effects of oxalate, a constituent of renal stones, on the growth of LLC-PK1 cells. Exposure to oxalate resulted in an initiation of DNA synthesis in serum-starved, growth-arrested cells as measured by 3H-thymidine incorporation. The effects of oxalate were comparable to those observed in response to 10% serum. Moreover, exposure to oxalate plus 10% serum stimulated DNA synthesis to a greater extent than oxalate or serum alone. These studies indicate that oxalate promotes the progression of cells from the G0/G1 to the S phase of the cell cycle. However, the increase in DNA synthesis was not always followed by an increase in cell number since high concentrations of oxalate led to a reduction in cell number.
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              The Dependence on Membrane Fluidity of Calcium Oxalate Crystal Attachment to IMCD Membranes

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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                978-3-8055-6818-0
                978-3-318-00390-1
                1660-8151
                2235-3186
                1999
                December 1998
                24 December 1998
                : 81
                : Suppl 1
                : 8-17
                Affiliations
                Departments of aMedicine and bPathology, University of Chicago, Ill., USA; cInstitute of Mineralogy, University of Palermo, Italy
                Article
                46293 Nephron 1999;81(suppl 1):8–17
                10.1159/000046293
                9873209
                © 1998 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: 3, Tables: 1, References: 55, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/46293
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