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      Phosphate Binder Impact on Bone Remodeling and Coronary Calcification – Results from the BRiC Study

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          Abstract

          Background and Aims: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. Methods: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. Results: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 ± 352 vs. 326 ± 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 ± 24 vs. 28 ± 15 U/l, p = 0.03) and deoxypyridinoline (135 ± 107 vs. 89 ± 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 ± 21 vs. 91 ± 28 mg/dl, p = 0.015). Phosphorus (5.8 ± 1.0 vs. 6 ± 1.0 mg/dl, p = 0.47) and calcium (1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078, p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm<sup>3</sup>/μm<sup>2</sup>/day, p = 0.010 for sevelamer). Conclusions: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups.

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          Most cited references22

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          Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee.

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            Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.

            The purpose of this study was to assess the value of electron beam computed tomography in the detection of cardiac calcifications in coronaries and valves of dialysis patients and to determine the rate at which calcification progresses. Forty-nine chronic hemodialysis patients aged 28 to 74 years were compared with 102 non-dialysis patients aged 32 to 73 years with documented or suspected coronary artery disease, all of whom underwent coronary angiography. We used high-resolution electron beam computed tomography scanning to make 30 axial slices with a distance of 3 mm between each slice. The number of calcifications, the surface area, and the average and highest density values were measured. We calculated a quantitative coronary artery calcium score and assessed calcification of mitral and aortic valves. In dialysis patients, the measurements were repeated after 12 months. The coronary artery calcium score was from 2.5-fold to fivefold higher in the dialysis patients than in the non-dialysis patients. Hypertensive dialysis patients had higher calcium scores than non-hypertensive dialysis patients (P < 0.05). A stepwise, multiple regression analysis confirmed the importance of age and hypertension. No correlation between calcium, phosphate, or parathyroid hormone values and the coronary calcium score was identified; however, the calcium score was inversely correlated with bone mass in the dialysis patients (r = 0.47, P < 0.05). The mitral valve was calcified in 59% of dialysis patients, while the aortic valve was calcified in 55%. The coronary artery calcium score was correlated with aortic valvular, but not mitral valvular calcification. A repeat examination of the dialysis patients at an interval of 1 year showed a disturbing tendency for progression. Our data under-score the frequency and severity of coronary and valvular calcifications in dialysis patients, and illustrate the rapid progression of this calcification. Finally, they draw attention to hypertension as an important risk factor in this process.
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              Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States.

              Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion. Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L). Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2008
                November 2008
                12 November 2008
                : 110
                : 4
                : c273-c283
                Affiliations
                Division of Nephrology, Department of Internal Medicine, aFederal University of São Paulo and bUniversity of São Paulo, and cThe Lipid Clinic of the Instituto do Coração (InCor, Heart Institute), University of São Paulo, São Paulo, Brazil
                Article
                170783 Nephron Clin Pract 2008;110:c273
                10.1159/000170783
                19001830
                ae57203b-2ecb-4978-a9df-cc0bf5d87869
                © 2008 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
                : 01 April 2008
                : 16 July 2008
                Page count
                Figures: 4, Tables: 6, References: 33, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Cardiovascular disease,Hemodialysis,Phosphate binders,Renal osteodystrophy,Vascular calcification

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