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      A High Calcium-Phosphate Product Is Associated with High C-Reactive Protein Concentrations in Hemodialysis Patients

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          Abstract

          Background: An elevated Ca×PO<sub>4</sub> product and C-reactive protein (CRP) have been associated with coronary artery calcification and increased cardiovascular mortality in hemodialysis (HD) patients. However, it has not been defined, so far, whether and how both parameters are related to each other. For this reason we have evaluated in a cross-sectional and in an interventional study the possible correlation between Ca×PO<sub>4</sub> and CRP and the effect of the correction of a high Ca×PO<sub>4</sub> on CRP levels. Methods: 47 uremic patients (age 65 ± 16 years) on regular chronic HD were selected from a total population of 125 prevalent patients treated at our Institution. Patients had no clinical evidence of either acute infectious or inflammatory diseases for at least 4 weeks before the study. They were on regular bicarbonate HD for 6–329 months (median 42). CRP, hemoglobin (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca), serum phosphorus (PO<sub>4</sub>), Ca×PO<sub>4</sub>, intact PTH, Kt/V, presence of ischemic heart disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln-transformed in all statistical analyses because of positive skewness. Results: The main findings were: LnCRP 2.17 ± 0.77 mg/l, Ca 10.1 ± 0.4 mg/dl, PO<sub>4</sub> 5.8 ± 0.6 mg/dl, Ca×PO<sub>4</sub> 59 ± 6 mg<sup>2</sup>/dl<sup>2</sup>, andPTHint 218 ± 195 ng/ml. 18/47 had IHD, 18/47 PVD. A significant hyperbolic correlation between Ca×PO<sub>4</sub> and CRP was observed. A piecewise linear regression model analysis identified a break-point for Ca×PO<sub>4</sub> at 55 mg<sup>2</sup>/dl<sup>2</sup>. Comparison of CRP levels after the division of the patients into two groups according to Ca×PO<sub>4</sub> break-point (group A, Ca×PO<sub>4</sub> ≤55 mg<sup>2</sup>/dl<sup>2</sup>, n = 16 patients; group B, Ca×PO<sub>4</sub> >55 mg<sup>2</sup>/dl<sup>2</sup>, n = 31 patients) showed that CRP levels were significantly lower in patients in group A (LnCRP 1.43 ± 0.22 mg/l) than in group B (LnCRP 2.55 ± 0.67 mg/l, p < 0.0001). Multiple regression analysis bearing LnCRP as dependent variable confirmed Ca×PO<sub>4</sub> as the most significant variable among the other variables examined. In 22 patients with Ca×PO<sub>4</sub> ≧60 mg<sup>2</sup>/dl<sup>2</sup>, we performed intensive lowering of the Ca×PO<sub>4</sub> product in order to reach and maintain a Ca×PO<sub>4</sub> ≤55 mg<sup>2</sup>/dl<sup>2</sup> for 3 months. At the end of observation, a significant reduction in Ca×PO<sub>4</sub> and LnCRP was observed (Ca×PO<sub>4</sub> pre 62.8 ± 1.9 vs. post 46.3 ± 6.2 mg<sup>2</sup>/dl<sup>2</sup>: p < 0.0001; LnCRP pre 2.32 ± 0.36 vs. post 1.83 ± 0.14 mg/l: p < 0.0001). No significant variation in the other biochemical parameters was observed. Conclusions: Our data show that in chronic HD patients in steady clinical conditions with no clinical evidence of either infectious or inflammatory diseases, a high Ca×PO<sub>4</sub> is associated with high CRP concentrations. Intensive lowering of Ca×PO<sub>4</sub> reduces CRP.

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          Most cited references 11

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          Coronary artery disease in end-stage renal disease: no longer a simple plumbing problem.

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            Cardiac Valve Calcification as an Important Predictor for All-Cause Mortality and Cardiovascular Mortality in Long-Term Peritoneal Dialysis Patients: A Prospective Study

             A. Wang (2003)
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              Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients.

              Short-term studies have suggested that sevelamer hydrochloride, a non-aluminium- and non-calcium-containing hydrogel, is an effective phosphate binder in haemodialysis patients, and may produce favourable changes in the lipid profile. To determine the long-term effectiveness of sevelamer hydrochloride, we performed an open-label clinical trial in 192 adult patients with end-stage renal disease on haemodialysis. Drug-related changes in the concentrations of serum phosphorus, calcium, calcium x phosphate product, parathyroid hormone, and low- and high-density lipoprotein cholesterol concentrations were the major outcomes of interest. Treatment with sevelamer was associated with a mean change in serum phosphorus of -0.71+/-0.77 mmol/l, serum calcium of 0. 08+/-0.22 mmol/l, and calcium x phosphate product of -1.46+/-1.78 mmol/l (P<0.0001 for all comparisons). There were no significant overall treatment-related changes in parathyroid hormone. Serum levels of LDL cholesterol decreased by 0.81+/-0.75 mmol/l (mean -30%, P<0.0001) and HDL cholesterol increased by a mean of 0.15+/-0.29 mmol/l (mean +18%, P<0.0001). Drug-related adverse events were infrequent and most were of mild intensity. Sevelamer is a safe and effective phosphate binder that leads to significant improvements in the calcium x phosphate product and lipid profile of haemodialysis patients.
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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
                2005
                December 2005
                10 August 2005
                : 101
                : 4
                : c161-c167
                Affiliations
                aChair and Division of Nephrology, Spedali Civili and University of Brescia, and bSection of Medical Statistics, Department of Biosciences, University of Brescia, Brescia, Italy
                Article
                87391 Nephron Clin Pract 2005;101:c161–c167
                10.1159/000087391
                16103720
                © 2005 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: 2, Tables: 6, References: 25, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87391
                Categories
                Editorial Review

                Cardiovascular Medicine, Nephrology

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