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Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid

Identifieur interne : 007585 ( Main/Exploration ); précédent : 007584; suivant : 007586

Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid

Auteurs : Teun Van Gelder [Pays-Bas] ; Helio Tedesco Silva [Brésil] ; Johan W. De Fijter [Pays-Bas] ; Klemens Budde [Allemagne] ; Dirk Kuypers [Belgique] ; Wolfgang Arns [Allemagne] ; Jean Paul Soulillou [France] ; John Kanellis [Australie] ; Arunas Zelvys [Lituanie] ; Henrik Ekberg [Suède] ; Herwig Holzer [Autriche] ; Lionel Rostaing [France] ; Richard D. Mamelok [États-Unis]

Source :

RBID : Pascal:10-0171377

Descripteurs français

English descriptors

Abstract

Background. To better define subpopulations in which achieving adequate mycophenolic acid (MPA) concentrations quickly would be important, a post hoc exploratory analysis on the fixed-dose concentration-controlled database was performed, comparing high- versus low-risk renal transplant patients. Methods. Renal transplant patients were treated with mycophenolate mofetil, corticosteroids, and cyclosporine A or tacrolimus. Patients were defined as "high risk" if they had one or more of the following characteristics: delayed graft function, second or third transplantation, panel reactive antibodies >15%, four or more human leukocyte antigen mismatches, or were of black race. Results. A total of 549 patients (61%) were classified as high risk, of whom 284 were on cyclosporine A treatment and 265 on tacrolimus. In high-risk patients, the difference in rejection incidence was 14.3% in the MPA-area under the concentration (AUC) less than 30 mg hr/L vs. 7.8% in the MPA-AUC more than or equal to 30 mg hr/L groups (P=0.025) during the first month after transplantation; whereas, in low-risk patients, there were similar rejection rates (5.7% vs. 4.5%). In the subgroup of high-risk tacrolimus-treated patients, the difference in acute rejection incidence in the first month between patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was most pronounced: 16 of 67 patients (23.9%) vs. 18 of 173 patients (10.4%); P=0.012. Conclusions. The incidence of acute rejection is higher in high-risk patients if MPA-AUC0-12 is below 30 mg hr/L. In contrast, a difference in acute rejection incidence in low-risk patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was not observed. This supports the use of a higher mycophenolate mofetil starting dose in selected patient populations early after transplantation.


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Le document en format XML

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<name sortKey="De Fijter, Johan W" sort="De Fijter, Johan W" uniqKey="De Fijter J" first="Johan W." last="De Fijter">Johan W. De Fijter</name>
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<wicri:noRegion>Department of Nephrology, Leiden University Medical Center</wicri:noRegion>
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<name sortKey="Budde, Klemens" sort="Budde, Klemens" uniqKey="Budde K" first="Klemens" last="Budde">Klemens Budde</name>
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<region type="land" nuts="3">Berlin</region>
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<name sortKey="Kuypers, Dirk" sort="Kuypers, Dirk" uniqKey="Kuypers D" first="Dirk" last="Kuypers">Dirk Kuypers</name>
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<s1>Department of Nephrology and Renal Transplantation, Leuven University</s1>
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<country>Belgique</country>
<wicri:noRegion>Department of Nephrology and Renal Transplantation, Leuven University</wicri:noRegion>
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<name sortKey="Arns, Wolfgang" sort="Arns, Wolfgang" uniqKey="Arns W" first="Wolfgang" last="Arns">Wolfgang Arns</name>
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<name sortKey="Soulillou, Jean Paul" sort="Soulillou, Jean Paul" uniqKey="Soulillou J" first="Jean Paul" last="Soulillou">Jean Paul Soulillou</name>
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<name sortKey="Zelvys, Arunas" sort="Zelvys, Arunas" uniqKey="Zelvys A" first="Arunas" last="Zelvys">Arunas Zelvys</name>
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<name sortKey="Ekberg, Henrik" sort="Ekberg, Henrik" uniqKey="Ekberg H" first="Henrik" last="Ekberg">Henrik Ekberg</name>
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<name sortKey="Mamelok, Richard D" sort="Mamelok, Richard D" uniqKey="Mamelok R" first="Richard D." last="Mamelok">Richard D. Mamelok</name>
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<title xml:lang="en" level="a">Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid</title>
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<name sortKey="Van Gelder, Teun" sort="Van Gelder, Teun" uniqKey="Van Gelder T" first="Teun" last="Van Gelder">Teun Van Gelder</name>
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<s1>Department of Hospital Pharmacy, Erasmus Medical Center</s1>
<s2>Rotterdam</s2>
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<sZ>1 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
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<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
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<s1>Department of Internal Medicine, Erasmus Medical Center</s1>
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<s3>NLD</s3>
<sZ>1 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
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<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
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<name sortKey="Tedesco Silva, Helio" sort="Tedesco Silva, Helio" uniqKey="Tedesco Silva H" first="Helio" last="Tedesco Silva">Helio Tedesco Silva</name>
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<s1>Department of Nephrology, Hospital do Rim e Hipertensao</s1>
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<s3>BRA</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
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<settlement type="city">São Paulo</settlement>
<region type="state">État de São Paulo</region>
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</affiliation>
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<name sortKey="De Fijter, Johan W" sort="De Fijter, Johan W" uniqKey="De Fijter J" first="Johan W." last="De Fijter">Johan W. De Fijter</name>
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<inist:fA14 i1="04">
<s1>Department of Nephrology, Leiden University Medical Center</s1>
<s3>NLD</s3>
<sZ>3 aut.</sZ>
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<country>Pays-Bas</country>
<wicri:noRegion>Department of Nephrology, Leiden University Medical Center</wicri:noRegion>
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<name sortKey="Budde, Klemens" sort="Budde, Klemens" uniqKey="Budde K" first="Klemens" last="Budde">Klemens Budde</name>
<affiliation wicri:level="3">
<inist:fA14 i1="05">
<s1>Department of Nephrology, Charité University</s1>
<s2>Berlin</s2>
<s3>DEU</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
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<name sortKey="Kuypers, Dirk" sort="Kuypers, Dirk" uniqKey="Kuypers D" first="Dirk" last="Kuypers">Dirk Kuypers</name>
<affiliation wicri:level="1">
<inist:fA14 i1="06">
<s1>Department of Nephrology and Renal Transplantation, Leuven University</s1>
<s3>BEL</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Belgique</country>
<wicri:noRegion>Department of Nephrology and Renal Transplantation, Leuven University</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Arns, Wolfgang" sort="Arns, Wolfgang" uniqKey="Arns W" first="Wolfgang" last="Arns">Wolfgang Arns</name>
<affiliation wicri:level="1">
<inist:fA14 i1="07">
<s1>Department of Transplantation, Merheim General Center</s1>
<s2>Cologne</s2>
<s3>DEU</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<wicri:noRegion>Cologne</wicri:noRegion>
<wicri:noRegion>Merheim General Center</wicri:noRegion>
<wicri:noRegion>Cologne</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Soulillou, Jean Paul" sort="Soulillou, Jean Paul" uniqKey="Soulillou J" first="Jean Paul" last="Soulillou">Jean Paul Soulillou</name>
<affiliation wicri:level="3">
<inist:fA14 i1="08">
<s1>Institute of Transplantation, Centre Hospitalier Universitair, University of Nantes</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kanellis, John" sort="Kanellis, John" uniqKey="Kanellis J" first="John" last="Kanellis">John Kanellis</name>
<affiliation wicri:level="1">
<inist:fA14 i1="09">
<s1>Department of Nephrology, Monash Medical Centre</s1>
<s2>Clayton, Victoria</s2>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Clayton, Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Zelvys, Arunas" sort="Zelvys, Arunas" uniqKey="Zelvys A" first="Arunas" last="Zelvys">Arunas Zelvys</name>
<affiliation wicri:level="1">
<inist:fA14 i1="10">
<s1>Department of Transplantation, Vilnius University Hospital Santariskiu Klinikos</s1>
<s2>Vilnius</s2>
<s3>LTU</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Lituanie</country>
<wicri:noRegion>Vilnius</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ekberg, Henrik" sort="Ekberg, Henrik" uniqKey="Ekberg H" first="Henrik" last="Ekberg">Henrik Ekberg</name>
<affiliation wicri:level="1">
<inist:fA14 i1="11">
<s1>Department of Nephrology and Transplantation, Lund University, University Hospital Malmö</s1>
<s3>SWE</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Suède</country>
<wicri:noRegion>Department of Nephrology and Transplantation, Lund University, University Hospital Malmö</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Holzer, Herwig" sort="Holzer, Herwig" uniqKey="Holzer H" first="Herwig" last="Holzer">Herwig Holzer</name>
<affiliation wicri:level="1">
<inist:fA14 i1="12">
<s1>Department of Nephrology, Medical University Graz</s1>
<s2>Graz</s2>
<s3>AUT</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Autriche</country>
<wicri:noRegion>Graz</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rostaing, Lionel" sort="Rostaing, Lionel" uniqKey="Rostaing L" first="Lionel" last="Rostaing">Lionel Rostaing</name>
<affiliation wicri:level="3">
<inist:fA14 i1="13">
<s1>Department of Nephrology and Multiorgan Transplantation, Hospital Rangueil</s1>
<s2>Toulouse</s2>
<s3>FRA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName>
<region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mamelok, Richard D" sort="Mamelok, Richard D" uniqKey="Mamelok R" first="Richard D." last="Mamelok">Richard D. Mamelok</name>
<affiliation wicri:level="1">
<inist:fA14 i1="14">
<s1>Mamelok Consulting</s1>
<s2>Palo Alto, CA</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Mamelok Consulting</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Transplantation</title>
<title level="j" type="abbreviated">Transplantation</title>
<idno type="ISSN">0041-1337</idno>
<imprint>
<date when="2010">2010</date>
</imprint>
</series>
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<seriesStmt>
<title level="j" type="main">Transplantation</title>
<title level="j" type="abbreviated">Transplantation</title>
<idno type="ISSN">0041-1337</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Acute</term>
<term>Antibiotic</term>
<term>Antiviral</term>
<term>Exposure</term>
<term>Graft</term>
<term>Graft(material)</term>
<term>High risk</term>
<term>Homotransplantation</term>
<term>Human</term>
<term>Immunomodulator</term>
<term>Immunosuppressive agent</term>
<term>Kidney</term>
<term>Mycophenolate mofetil</term>
<term>Mycophenolic acid</term>
<term>Patient</term>
<term>Rejection</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Homotransplantation</term>
<term>Rein</term>
<term>Homme</term>
<term>Acide mycophénolique</term>
<term>Malade</term>
<term>Risque élevé</term>
<term>Mycophénolate mofétil</term>
<term>Aigu</term>
<term>Rejet</term>
<term>Greffon</term>
<term>Exposition</term>
<term>Greffe</term>
<term>Immunomodulateur</term>
<term>Immunodépresseur</term>
<term>Antiviral</term>
<term>Antibiotique</term>
<term>Traitement</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Homme</term>
<term>Antibiotique</term>
</keywords>
</textClass>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background. To better define subpopulations in which achieving adequate mycophenolic acid (MPA) concentrations quickly would be important, a post hoc exploratory analysis on the fixed-dose concentration-controlled database was performed, comparing high- versus low-risk renal transplant patients. Methods. Renal transplant patients were treated with mycophenolate mofetil, corticosteroids, and cyclosporine A or tacrolimus. Patients were defined as "high risk" if they had one or more of the following characteristics: delayed graft function, second or third transplantation, panel reactive antibodies >15%, four or more human leukocyte antigen mismatches, or were of black race. Results. A total of 549 patients (61%) were classified as high risk, of whom 284 were on cyclosporine A treatment and 265 on tacrolimus. In high-risk patients, the difference in rejection incidence was 14.3% in the MPA-area under the concentration (AUC) less than 30 mg hr/L vs. 7.8% in the MPA-AUC more than or equal to 30 mg hr/L groups (P=0.025) during the first month after transplantation; whereas, in low-risk patients, there were similar rejection rates (5.7% vs. 4.5%). In the subgroup of high-risk tacrolimus-treated patients, the difference in acute rejection incidence in the first month between patients with MPA-AUC
<sub>0-12</sub>
less than or more than or equal to 30 mg hr/L was most pronounced: 16 of 67 patients (23.9%) vs. 18 of 173 patients (10.4%); P=0.012. Conclusions. The incidence of acute rejection is higher in high-risk patients if MPA-AUC
<sub>0-12</sub>
is below 30 mg hr/L. In contrast, a difference in acute rejection incidence in low-risk patients with MPA-AUC
<sub>0-12</sub>
less than or more than or equal to 30 mg hr/L was not observed. This supports the use of a higher mycophenolate mofetil starting dose in selected patient populations early after transplantation.</div>
</front>
</TEI>
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<li>Allemagne</li>
<li>Australie</li>
<li>Autriche</li>
<li>Belgique</li>
<li>Brésil</li>
<li>France</li>
<li>Lituanie</li>
<li>Pays-Bas</li>
<li>Suède</li>
<li>États-Unis</li>
</country>
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<li>Berlin</li>
<li>Hollande-Méridionale</li>
<li>Midi-Pyrénées</li>
<li>Occitanie (région administrative)</li>
<li>Pays de la Loire</li>
<li>État de São Paulo</li>
</region>
<settlement>
<li>Berlin</li>
<li>Nantes</li>
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<li>São Paulo</li>
<li>Toulouse</li>
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<name sortKey="Van Gelder, Teun" sort="Van Gelder, Teun" uniqKey="Van Gelder T" first="Teun" last="Van Gelder">Teun Van Gelder</name>
</country>
<country name="Brésil">
<region name="État de São Paulo">
<name sortKey="Tedesco Silva, Helio" sort="Tedesco Silva, Helio" uniqKey="Tedesco Silva H" first="Helio" last="Tedesco Silva">Helio Tedesco Silva</name>
</region>
</country>
<country name="Allemagne">
<region name="Berlin">
<name sortKey="Budde, Klemens" sort="Budde, Klemens" uniqKey="Budde K" first="Klemens" last="Budde">Klemens Budde</name>
</region>
<name sortKey="Arns, Wolfgang" sort="Arns, Wolfgang" uniqKey="Arns W" first="Wolfgang" last="Arns">Wolfgang Arns</name>
</country>
<country name="Belgique">
<noRegion>
<name sortKey="Kuypers, Dirk" sort="Kuypers, Dirk" uniqKey="Kuypers D" first="Dirk" last="Kuypers">Dirk Kuypers</name>
</noRegion>
</country>
<country name="France">
<region name="Pays de la Loire">
<name sortKey="Soulillou, Jean Paul" sort="Soulillou, Jean Paul" uniqKey="Soulillou J" first="Jean Paul" last="Soulillou">Jean Paul Soulillou</name>
</region>
<name sortKey="Rostaing, Lionel" sort="Rostaing, Lionel" uniqKey="Rostaing L" first="Lionel" last="Rostaing">Lionel Rostaing</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Kanellis, John" sort="Kanellis, John" uniqKey="Kanellis J" first="John" last="Kanellis">John Kanellis</name>
</noRegion>
</country>
<country name="Lituanie">
<noRegion>
<name sortKey="Zelvys, Arunas" sort="Zelvys, Arunas" uniqKey="Zelvys A" first="Arunas" last="Zelvys">Arunas Zelvys</name>
</noRegion>
</country>
<country name="Suède">
<noRegion>
<name sortKey="Ekberg, Henrik" sort="Ekberg, Henrik" uniqKey="Ekberg H" first="Henrik" last="Ekberg">Henrik Ekberg</name>
</noRegion>
</country>
<country name="Autriche">
<noRegion>
<name sortKey="Holzer, Herwig" sort="Holzer, Herwig" uniqKey="Holzer H" first="Herwig" last="Holzer">Herwig Holzer</name>
</noRegion>
</country>
<country name="États-Unis">
<noRegion>
<name sortKey="Mamelok, Richard D" sort="Mamelok, Richard D" uniqKey="Mamelok R" first="Richard D." last="Mamelok">Richard D. Mamelok</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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