Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia
Identifieur interne : 000165 ( Ncbi/Merge ); précédent : 000164; suivant : 000166Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia
Auteurs : Tineke M. De Schutter [Belgique] ; Geert J. Behets [Belgique] ; Hilde Geryl [Belgique] ; Mirjam E. Peter [Allemagne] ; Sonja Steppan [Allemagne] ; Kristina Gundlach [Allemagne] ; Jutta Passlick-Deetjen [Allemagne] ; Patrick C. D'Haese [Belgique] ; Ellen Neven [Belgique]Source :
- Kidney International [ 0085-2538 ] ; 2013.
Abstract
Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased
Url:
DOI: 10.1038/ki.2013.34
PubMed: 23486515
PubMed Central: 3674404
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<front><div type="abstract" xml:lang="en"><p>Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased <italic>sox9</italic>
, <italic>bmp-2</italic>
, and <italic>matrix gla protein</italic>
expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.</p>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Kidney Int</journal-id>
<journal-id journal-id-type="iso-abbrev">Kidney Int</journal-id>
<journal-title-group><journal-title>Kidney International</journal-title>
</journal-title-group>
<issn pub-type="ppub">0085-2538</issn>
<issn pub-type="epub">1523-1755</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23486515</article-id>
<article-id pub-id-type="pmc">3674404</article-id>
<article-id pub-id-type="pii">ki201334</article-id>
<article-id pub-id-type="doi">10.1038/ki.2013.34</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Basic Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia</article-title>
<alt-title alt-title-type="running">A comparative multiple-dose study</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>De Schutter</surname>
<given-names>Tineke M</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Behets</surname>
<given-names>Geert J</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Geryl</surname>
<given-names>Hilde</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peter</surname>
<given-names>Mirjam E</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Steppan</surname>
<given-names>Sonja</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gundlach</surname>
<given-names>Kristina</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Passlick-Deetjen</surname>
<given-names>Jutta</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>D'Haese</surname>
<given-names>Patrick C</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Neven</surname>
<given-names>Ellen</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<aff id="aff1"><label>1</label>
<institution>Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp</institution>
, Antwerp,<country>Belgium</country>
</aff>
<aff id="aff2"><label>2</label>
<institution>Fresenius Medical Care Deutschland GmbH</institution>
, Bad Homburg,<country>Germany</country>
</aff>
<aff id="aff3"><label>3</label>
<institution>Department of Nephrology, University of Dusseldorf</institution>
, Dusseldorf,<country>Germany</country>
</aff>
</contrib-group>
<author-notes><corresp id="caf1"><label>*</label>
<institution>Laboratory of Pathophysiology, University of Antwerp, Campus Drie Eiken, Building T.0, Universiteitsplein 1</institution>
, Antwerp, B-2610, <country>Belgium</country>
. E-mail: <email>Patrick.dhaese@ua.ac.be</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>06</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>13</day>
<month>03</month>
<year>2013</year>
</pub-date>
<volume>83</volume>
<issue>6</issue>
<fpage>1109</fpage>
<lpage>1117</lpage>
<history><date date-type="received"><day>26</day>
<month>03</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>21</day>
<month>11</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>30</day>
<month>11</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2013 International Society of Nephrology</copyright-statement>
<copyright-year>2013</copyright-year>
<copyright-holder>International Society of Nephrology</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/</license-p>
</license>
</permissions>
<abstract><p>Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased <italic>sox9</italic>
, <italic>bmp-2</italic>
, and <italic>matrix gla protein</italic>
expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.</p>
</abstract>
<kwd-group><kwd>hyperphosphatemia</kwd>
<kwd>phosphate binders</kwd>
<kwd>vascular calcification</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="fig1"><label>Figure 1</label>
<caption><p><bold>Study setup.</bold>
CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev750, 750 mg/kg sevelamer.</p>
</caption>
<graphic xlink:href="ki201334f1"></graphic>
</fig>
<fig id="fig2"><label>Figure 2</label>
<caption><p><bold>Mineral metabolism.</bold>
(<bold>a</bold>
) Serum phosphorus, (<bold>b</bold>
) urinary phosphate, and (<bold>c</bold>
) serum ionized calcium concentrations throughout the study. Data are expressed as mean±s.d. Statistical differences are indicated in <xref rid="tbl1" ref-type="table">Table 1</xref>
.</p>
</caption>
<graphic xlink:href="ki201334f2"></graphic>
</fig>
<fig id="fig3"><label>Figure 3</label>
<caption><p><bold>Vascular calcification.</bold>
(<bold>a</bold>
) Calcium concentration in the aorta; (<bold>b</bold>
) area percent von Kossa positivity (% aortic calcification) in CRF rats treated with vehicle (<italic>n</italic>
=14), CaMg750 (<italic>n</italic>
=14), CaMg375 (<italic>n</italic>
=14), and Sev750 (<italic>n</italic>
=14). CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; CRF, chronic renal failure; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; Veh, vehicle. *Significant difference versus vehicle. Open symbols indicate the animals died before the day of killing.</p>
</caption>
<graphic xlink:href="ki201334f3"></graphic>
</fig>
<fig id="fig4"><label>Figure 4</label>
<caption><p><bold>Calcium X-ray fluorescence and X-ray diffraction patterns of the deposited mineral in the calcified aorta of a uremic rat treated with 375 mg/kg calcium acetate/magnesium carbonate (CaMg).</bold>
All groups showed similar diffraction patterns.</p>
</caption>
<graphic xlink:href="ki201334f4"></graphic>
</fig>
<fig id="fig5"><label>Figure 5</label>
<caption><p><bold>mRNA expression of the different target genes relative to glyceraldehyde 3-phosphate dehydrogenase (<italic>GAPDH</italic>
) in the aorta of rats with chronic renal failure (CRF) compared with rats with normal renal function (NRF).</bold>
The number of animals for each study group is indicated in the bars of <xref ref-type="fig" rid="fig1">Figure 1</xref>
. Data are expressed as mean±s.d. <italic>bmp-2</italic>
, bone morphogenic protein 2; CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; <italic>cbfa-1</italic>
core binding factor-α1; <italic>mgp</italic>
, matrix gla protein; <italic>Osx</italic>
, osterix; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; <italic>sox9</italic>
, sex determining region Y-box 9; <italic>TRPM7</italic>
, transient receptor potential cation channel, subfamily M, member 7; VC, vascular calcification; VK, von Kossa positivity. *Significant difference versus NRF; °significant difference versus VC of the same group.</p>
</caption>
<graphic xlink:href="ki201334f5"></graphic>
</fig>
<table-wrap id="tbl1"><label>Table 1</label>
<caption><title>Serum and urine biochemistry</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th>
<th colspan="5" align="center" valign="top" char="±" charoff="50"><bold>Weeks of CRF</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="char" valign="top" char="±" charoff="50"><bold>Baseline (</bold>
<italic><bold>n</bold>
</italic>
<bold>=14 per group)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>0 (</bold>
<italic><bold>n</bold>
</italic>
<bold>=14 per group)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>1 (</bold>
<italic><bold>n</bold>
</italic>
<bold>=7 per group)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>4 (</bold>
<italic><bold>n</bold>
</italic>
<bold>=7 per group)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>6 (</bold>
<italic><bold>n</bold>
</italic>
<bold>=14 per group)</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum creatinine (mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">0.28±0.02</td>
<td align="char" valign="top" char="±" charoff="50">0.32±0.05</td>
<td align="char" valign="top" char="±" charoff="50">0.66±0.16°</td>
<td align="char" valign="top" char="±" charoff="50">4.21±1.05°</td>
<td align="char" valign="top" char="±" charoff="50">2.11±0.60°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">0.27±0.04°</td>
<td align="char" valign="top" char="±" charoff="50">0.34±0.05</td>
<td align="char" valign="top" char="±" charoff="50">0.61±0.11°</td>
<td align="char" valign="top" char="±" charoff="50">4.10±0.98°</td>
<td align="char" valign="top" char="±" charoff="50">3.08±1.14*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">0.28±0.04</td>
<td align="char" valign="top" char="±" charoff="50">0.31±0.02</td>
<td align="char" valign="top" char="±" charoff="50">0.71±0.34°</td>
<td align="char" valign="top" char="±" charoff="50">4.11±0.78°</td>
<td align="char" valign="top" char="±" charoff="50">2.23±0.55°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">0.29±0.03</td>
<td align="char" valign="top" char="±" charoff="50">0.32±0.07</td>
<td align="char" valign="top" char="±" charoff="50">0.96±0.41°</td>
<td align="char" valign="top" char="±" charoff="50">4.11±1.07°</td>
<td align="char" valign="top" char="±" charoff="50">2.40±1.13°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum P (mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">7.01±0.78°</td>
<td align="char" valign="top" char="±" charoff="50">6.21±0.56</td>
<td align="char" valign="top" char="±" charoff="50">4.82±0.99°</td>
<td align="char" valign="top" char="±" charoff="50">20.34±12.01°</td>
<td align="char" valign="top" char="±" charoff="50">8.91±2.19°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">6.45±0.81</td>
<td align="char" valign="top" char="±" charoff="50">5.86±0.86</td>
<td align="char" valign="top" char="±" charoff="50">5.44±1.54</td>
<td align="char" valign="top" char="±" charoff="50">9.88±2.03*°</td>
<td align="char" valign="top" char="±" charoff="50">10.30±7.43°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">6.73±0.83</td>
<td align="char" valign="top" char="±" charoff="50">6.52±0.77</td>
<td align="char" valign="top" char="±" charoff="50">5.37±1.94</td>
<td align="char" valign="top" char="±" charoff="50">11.52±1.91°</td>
<td align="char" valign="top" char="±" charoff="50">7.30±2.28</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">6.75±0.78</td>
<td align="char" valign="top" char="±" charoff="50">6.47±1.12</td>
<td align="char" valign="top" char="±" charoff="50">6.06±1.75</td>
<td align="char" valign="top" char="±" charoff="50">16.26±9.20°</td>
<td align="char" valign="top" char="±" charoff="50">8.06±7.09*</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum Ca (mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">10.49±0.23</td>
<td align="char" valign="top" char="±" charoff="50">10.41±0.42</td>
<td align="char" valign="top" char="±" charoff="50">9.23±0.17°</td>
<td align="char" valign="top" char="±" charoff="50">9.68±0.58°</td>
<td align="char" valign="top" char="±" charoff="50">10.05±1.13</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">10.19±0.21*</td>
<td align="char" valign="top" char="±" charoff="50">10.44±0.65</td>
<td align="char" valign="top" char="±" charoff="50">9.33±0.16°</td>
<td align="char" valign="top" char="±" charoff="50">10.65±0.47*</td>
<td align="char" valign="top" char="±" charoff="50">11.51±1.25*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">10.49±0.25</td>
<td align="char" valign="top" char="±" charoff="50">10.36±0.48</td>
<td align="char" valign="top" char="±" charoff="50">9.22±0.25°</td>
<td align="char" valign="top" char="±" charoff="50">10.49±0.42</td>
<td align="char" valign="top" char="±" charoff="50">11.15±0.64*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">10.68±0.18*°</td>
<td align="char" valign="top" char="±" charoff="50">10.25±0.46</td>
<td align="char" valign="top" char="±" charoff="50">9.37±0.22°</td>
<td align="char" valign="top" char="±" charoff="50">10.12±0.74</td>
<td align="char" valign="top" char="±" charoff="50">10.99±0.55°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum Mg (mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">1.95±0.08°</td>
<td align="char" valign="top" char="±" charoff="50">1.74±0.05</td>
<td align="char" valign="top" char="±" charoff="50">1.70±0.09</td>
<td align="char" valign="top" char="±" charoff="50">2.80±0.28°</td>
<td align="char" valign="top" char="±" charoff="50">2.42±0.25°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">2.00±0.13°</td>
<td align="char" valign="top" char="±" charoff="50">1.77±0.14</td>
<td align="char" valign="top" char="±" charoff="50">1.90±0.24</td>
<td align="char" valign="top" char="±" charoff="50">6.82±0.77*°</td>
<td align="char" valign="top" char="±" charoff="50">5.44±1.68*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">1.90±0.14°</td>
<td align="char" valign="top" char="±" charoff="50">1.72±0.09</td>
<td align="char" valign="top" char="±" charoff="50">1.84±0.17</td>
<td align="char" valign="top" char="±" charoff="50">4.99±0.55*°</td>
<td align="char" valign="top" char="±" charoff="50">3.37±0.51*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">1.85±0.12*</td>
<td align="char" valign="top" char="±" charoff="50">1.79±0.15</td>
<td align="char" valign="top" char="±" charoff="50">1.97±0.15*°</td>
<td align="char" valign="top" char="±" charoff="50">2.74±0.23°</td>
<td align="char" valign="top" char="±" charoff="50">2.78±0.44°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum Ca</italic>
<sup><italic>2</italic>
+</sup>
<italic>(mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">5.26±0.13</td>
<td align="char" valign="top" char="±" charoff="50">5.20±0.20</td>
<td align="char" valign="top" char="±" charoff="50">4.94±0.08°</td>
<td align="char" valign="top" char="±" charoff="50">4.39±0.34°</td>
<td align="char" valign="top" char="±" charoff="50">4.23±0.59°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">5.32±0.10</td>
<td align="char" valign="top" char="±" charoff="50">5.20±0.13</td>
<td align="char" valign="top" char="±" charoff="50">5.04±0.16</td>
<td align="char" valign="top" char="±" charoff="50">4.17±0.15°</td>
<td align="char" valign="top" char="±" charoff="50">4.46±0.34°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">5.29±0.16</td>
<td align="char" valign="top" char="±" charoff="50">5.19±0.11</td>
<td align="char" valign="top" char="±" charoff="50">4.90±0.13°</td>
<td align="char" valign="top" char="±" charoff="50">4.38±0.16°</td>
<td align="char" valign="top" char="±" charoff="50">4.68±0.25°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">5.32±0.09</td>
<td align="char" valign="top" char="±" charoff="50">5.24±0.10</td>
<td align="char" valign="top" char="±" charoff="50">4.96±0.20°</td>
<td align="char" valign="top" char="±" charoff="50">4.44±0.36°</td>
<td align="char" valign="top" char="±" charoff="50">4.55±0.40°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum PTH (pg/ml)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">213.0±1876</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">814.9±361.4°</td>
<td align="char" valign="top" char="±" charoff="50">1109.3±270.9°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">209.7±148.9</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">46.3±18.8*°</td>
<td align="char" valign="top" char="±" charoff="50">325.2±293.2*</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">164.4±48.5</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">328.3±169.7</td>
<td align="char" valign="top" char="±" charoff="50">605.6±499.3°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">198.1±67.0</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">677.4±136.8°</td>
<td align="char" valign="top" char="±" charoff="50">963.6±648.1°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum iFGF-23 (ng/ml)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">0.30±0.05</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">0.38±0.10</td>
<td align="char" valign="top" char="±" charoff="50">166±192°</td>
<td align="char" valign="top" char="±" charoff="50">110±128°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">0.32±0.09</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">0.47±0.22</td>
<td align="char" valign="top" char="±" charoff="50">47.4±52.6°</td>
<td align="char" valign="top" char="±" charoff="50">277±148*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">0.26±0.09</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">0.71±0.58</td>
<td align="char" valign="top" char="±" charoff="50">87.7±65.4°</td>
<td align="char" valign="top" char="±" charoff="50">217±219°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">0.30±0.09</td>
<td align="char" valign="top" char="±" charoff="50"> </td>
<td align="char" valign="top" char="±" charoff="50">0.87±0.66</td>
<td align="char" valign="top" char="±" charoff="50">75.3±61.6°</td>
<td align="char" valign="top" char="±" charoff="50">99±157°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum pH</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">7.39±0.04</td>
<td align="char" valign="top" char="±" charoff="50">7.41±0.05</td>
<td align="char" valign="top" char="±" charoff="50">7.48±0.06°</td>
<td align="char" valign="top" char="±" charoff="50">7.46±0.09</td>
<td align="char" valign="top" char="±" charoff="50">7.52±0.07°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">7.39±0.06</td>
<td align="char" valign="top" char="±" charoff="50">7.41±0.04</td>
<td align="char" valign="top" char="±" charoff="50">7.46±0.05</td>
<td align="char" valign="top" char="±" charoff="50">7.57±0.05*°</td>
<td align="char" valign="top" char="±" charoff="50">7.60±0.05*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">7.42±0.03</td>
<td align="char" valign="top" char="±" charoff="50">7.44±0.05</td>
<td align="char" valign="top" char="±" charoff="50">7.52±0.04°</td>
<td align="char" valign="top" char="±" charoff="50">7.53±0.06°</td>
<td align="char" valign="top" char="±" charoff="50">7.60±0.05*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">7.40±0.05</td>
<td align="char" valign="top" char="±" charoff="50">7.42±0.04</td>
<td align="char" valign="top" char="±" charoff="50">7.49±0.08</td>
<td align="char" valign="top" char="±" charoff="50">7.48±0.05°</td>
<td align="char" valign="top" char="±" charoff="50">7.56±0.06°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Serum HCO</italic>
<sub><italic>3</italic>
</sub>
<sup>−</sup>
<italic>(mg/dl)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">25.6±1.0</td>
<td align="char" valign="top" char="±" charoff="50">26.4±2.0</td>
<td align="char" valign="top" char="±" charoff="50">27.4±2.2</td>
<td align="char" valign="top" char="±" charoff="50">25.0±4.3</td>
<td align="char" valign="top" char="±" charoff="50">30.0±2.9°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">25.1±0.9</td>
<td align="char" valign="top" char="±" charoff="50">25.2±2.1</td>
<td align="char" valign="top" char="±" charoff="50">27.0±2.9</td>
<td align="char" valign="top" char="±" charoff="50">33.8±2.7*°</td>
<td align="char" valign="top" char="±" charoff="50">37.0±5.0*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">26.4±1.7</td>
<td align="char" valign="top" char="±" charoff="50">26.9±1.8</td>
<td align="char" valign="top" char="±" charoff="50">28.4±1.9</td>
<td align="char" valign="top" char="±" charoff="50">29.5±4.5</td>
<td align="char" valign="top" char="±" charoff="50">35.0±2.6*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">25.3±1.6</td>
<td align="char" valign="top" char="±" charoff="50">26.1±1.4</td>
<td align="char" valign="top" char="±" charoff="50">26.6±2.5</td>
<td align="char" valign="top" char="±" charoff="50">26.1±0.6</td>
<td align="char" valign="top" char="±" charoff="50">32.1±3.4°</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Urine P (g/g creatinine)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">8.45±2.68</td>
<td align="char" valign="top" char="±" charoff="50">7.12±1.18</td>
<td align="char" valign="top" char="±" charoff="50">0.94±0.90°</td>
<td align="char" valign="top" char="±" charoff="50">5.17±1.37°</td>
<td align="char" valign="top" char="±" charoff="50">10.73±2.36°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">7.66±1.61</td>
<td align="char" valign="top" char="±" charoff="50">7.91±1.72</td>
<td align="char" valign="top" char="±" charoff="50">1.05±0.62°</td>
<td align="char" valign="top" char="±" charoff="50">1.85±0.89*°</td>
<td align="char" valign="top" char="±" charoff="50">5.27±7.05*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg 375</td>
<td align="char" valign="top" char="±" charoff="50">7.04±1.67</td>
<td align="char" valign="top" char="±" charoff="50">7.35±1.84</td>
<td align="char" valign="top" char="±" charoff="50">1.33±0.78°</td>
<td align="char" valign="top" char="±" charoff="50">2.77±1.08*°</td>
<td align="char" valign="top" char="±" charoff="50">6.46±2.82*</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">7.14±2.07</td>
<td align="char" valign="top" char="±" charoff="50">8.06±1.89</td>
<td align="char" valign="top" char="±" charoff="50">1.74±1.63°</td>
<td align="char" valign="top" char="±" charoff="50">3.90±1.54°</td>
<td align="char" valign="top" char="±" charoff="50">6.25±1.89*</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Urine Ca (mg/g creatinine)</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Vehicle</td>
<td align="char" valign="top" char="±" charoff="50">1.45±0.38°</td>
<td align="char" valign="top" char="±" charoff="50">0.97±0.31</td>
<td align="char" valign="top" char="±" charoff="50">0.90±0.06</td>
<td align="char" valign="top" char="±" charoff="50">10.21±3.46°</td>
<td align="char" valign="top" char="±" charoff="50">25.65±10.88°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg750</td>
<td align="char" valign="top" char="±" charoff="50">1.62±0.74</td>
<td align="char" valign="top" char="±" charoff="50">1.38±0.93</td>
<td align="char" valign="top" char="±" charoff="50">0.98±0.28</td>
<td align="char" valign="top" char="±" charoff="50">10.61±3.49°</td>
<td align="char" valign="top" char="±" charoff="50">13.29±7.05*°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> CaMg375</td>
<td align="char" valign="top" char="±" charoff="50">1.65±0.88</td>
<td align="char" valign="top" char="±" charoff="50">1.32±0.55</td>
<td align="char" valign="top" char="±" charoff="50">0.90±0.40</td>
<td align="char" valign="top" char="±" charoff="50">11.74±7.41°</td>
<td align="char" valign="top" char="±" charoff="50">27.08±20.41°</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Sev750</td>
<td align="char" valign="top" char="±" charoff="50">1.59±0.90</td>
<td align="char" valign="top" char="±" charoff="50">1.03±0.36°</td>
<td align="char" valign="top" char="±" charoff="50">0.87±0.33</td>
<td align="char" valign="top" char="±" charoff="50">11.39±3.81°</td>
<td align="char" valign="top" char="±" charoff="50">25.58±19.71°</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t1-fn1"><p>Abbreviations: CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; CRF, chronic renal failure; iFGF-23, intact fibroblast growth factor 23; PTH, parathyroid hormone; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg.</p>
</fn>
<fn id="t1-fn2"><p>*Significant difference versus vehicle at the same time point.</p>
</fn>
<fn id="t1-fn3"><p>°Significant difference versus week 0 of the same group.</p>
</fn>
<fn id="t1-fn4"><p>Biochemical parameters are measured in serum and urine.</p>
</fn>
<fn id="t1-fn5"><p>Data are expressed as mean±s.d.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl2"><label>Table 2</label>
<caption><title>Calcium and magnesium content in the aorta, carotid and femoral arteries</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th>
<th colspan="3" align="center" valign="top" char="±" charoff="50"><bold>Aorta</bold>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" char="±" charoff="50"><bold>Carotid artery</bold>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" char="±" charoff="50"><bold>Femoral artery</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="char" valign="top" char="±" charoff="50"><bold>Ca (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg/Ca ratio</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Ca (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg/Ca ratio</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Ca (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg (mg/g)</bold>
</th>
<th align="char" valign="top" char="±" charoff="50"><bold>Mg/Ca ratio</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">Vehicle (<italic>n</italic>
=14)</td>
<td align="char" valign="top" char="±" charoff="50">54.5±29.7</td>
<td align="char" valign="top" char="±" charoff="50">2.75±1.66</td>
<td align="char" valign="top" char="±" charoff="50">0.072±0.064</td>
<td align="char" valign="top" char="±" charoff="50">24.2±19.1</td>
<td align="char" valign="top" char="±" charoff="50">2.19±1.41</td>
<td align="char" valign="top" char="±" charoff="50">0.084±0.016</td>
<td align="char" valign="top" char="±" charoff="50">6.50±3.78</td>
<td align="char" valign="top" char="±" charoff="50">0.71±0.34</td>
<td align="char" valign="top" char="±" charoff="50">0.112±0.018</td>
</tr>
<tr><td align="left" valign="top" charoff="50">CaMg750 (<italic>n</italic>
=14)</td>
<td align="char" valign="top" char="±" charoff="50">24.9±16.5*</td>
<td align="char" valign="top" char="±" charoff="50">2.72±1.61</td>
<td align="char" valign="top" char="±" charoff="50">0.137±0.065*</td>
<td align="char" valign="top" char="±" charoff="50">21.3±18.5</td>
<td align="char" valign="top" char="±" charoff="50">3.33±2.22*</td>
<td align="char" valign="top" char="±" charoff="50">0.160±0.090*</td>
<td align="char" valign="top" char="±" charoff="50">6.98±3.84</td>
<td align="char" valign="top" char="±" charoff="50">1.19±0.55</td>
<td align="char" valign="top" char="±" charoff="50">0.194±0.091*</td>
</tr>
<tr><td align="left" valign="top" charoff="50">CaMg375 (<italic>n</italic>
=14)</td>
<td align="char" valign="top" char="±" charoff="50">17.8±13.2*</td>
<td align="char" valign="top" char="±" charoff="50">1.84±1.44</td>
<td align="char" valign="top" char="±" charoff="50">0.135±0.074*</td>
<td align="char" valign="top" char="±" charoff="50">14.9±16.4</td>
<td align="char" valign="top" char="±" charoff="50">1.98±2.02</td>
<td align="char" valign="top" char="±" charoff="50">0.188±0.134*</td>
<td align="char" valign="top" char="±" charoff="50">4.69±3.60</td>
<td align="char" valign="top" char="±" charoff="50">0.66±0.42</td>
<td align="char" valign="top" char="±" charoff="50">0.149±0.042*</td>
</tr>
<tr><td align="left" valign="top" charoff="50">Sev750 (<italic>n</italic>
=14)</td>
<td align="char" valign="top" char="±" charoff="50">33.4±34.2</td>
<td align="char" valign="top" char="±" charoff="50">1.98±1.81</td>
<td align="char" valign="top" char="±" charoff="50">0.128±0.103</td>
<td align="char" valign="top" char="±" charoff="50">8.0±12.1*</td>
<td align="char" valign="top" char="±" charoff="50">1.09±1.14</td>
<td align="char" valign="top" char="±" charoff="50">0.200±0.165*</td>
<td align="char" valign="top" char="±" charoff="50">2.79±4.70</td>
<td align="char" valign="top" char="±" charoff="50">0.52±0.50*</td>
<td align="char" valign="top" char="±" charoff="50">0.165±0.079*</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t2-fn1"><p>Abbreviations: CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg.</p>
</fn>
<fn id="t2-fn2"><p>*Significant difference versus vehicle.</p>
</fn>
<fn id="t2-fn3"><p>Data are expressed as mean±s.d.</p>
</fn>
<fn id="t2-fn4"><p>Tissue calcium, magnesium concentration, and Mg/Ca ratio in the different blood vessels.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Belgique</li>
</country>
</list>
<tree><country name="Belgique"><noRegion><name sortKey="De Schutter, Tineke M" sort="De Schutter, Tineke M" uniqKey="De Schutter T" first="Tineke M" last="De Schutter">Tineke M. De Schutter</name>
</noRegion>
<name sortKey="Behets, Geert J" sort="Behets, Geert J" uniqKey="Behets G" first="Geert J" last="Behets">Geert J. Behets</name>
<name sortKey="D Haese, Patrick C" sort="D Haese, Patrick C" uniqKey="D Haese P" first="Patrick C" last="D'Haese">Patrick C. D'Haese</name>
<name sortKey="Geryl, Hilde" sort="Geryl, Hilde" uniqKey="Geryl H" first="Hilde" last="Geryl">Hilde Geryl</name>
<name sortKey="Neven, Ellen" sort="Neven, Ellen" uniqKey="Neven E" first="Ellen" last="Neven">Ellen Neven</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Peter, Mirjam E" sort="Peter, Mirjam E" uniqKey="Peter M" first="Mirjam E" last="Peter">Mirjam E. Peter</name>
</noRegion>
<name sortKey="Gundlach, Kristina" sort="Gundlach, Kristina" uniqKey="Gundlach K" first="Kristina" last="Gundlach">Kristina Gundlach</name>
<name sortKey="Passlick Deetjen, Jutta" sort="Passlick Deetjen, Jutta" uniqKey="Passlick Deetjen J" first="Jutta" last="Passlick-Deetjen">Jutta Passlick-Deetjen</name>
<name sortKey="Steppan, Sonja" sort="Steppan, Sonja" uniqKey="Steppan S" first="Sonja" last="Steppan">Sonja Steppan</name>
</country>
</tree>
</affiliations>
</record>
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