Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.
Identifieur interne : 000580 ( Main/Exploration ); précédent : 000579; suivant : 000581Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.
Auteurs : Z. Daher Abdi [France] ; M. Essig ; D. Rizopoulos ; Y. Le Meur ; A. Prémaud ; J B Woillard ; J P Rérolle ; P. Marquet ; A. RousseauSource :
- Pharmacological research ; 2013.
English descriptors
- KwdEn :
- Adult, Age Factors, Aged, Graft Rejection (chemically induced), Humans, Immunosuppressive Agents (administration & dosage), Immunosuppressive Agents (adverse effects), Immunosuppressive Agents (therapeutic use), Kidney Transplantation (methods), Middle Aged, Models, Biological, Mycophenolic Acid (administration & dosage), Mycophenolic Acid (adverse effects), Mycophenolic Acid (therapeutic use), ROC Curve.
- MESH :
- chemical , administration & dosage : Immunosuppressive Agents, Mycophenolic Acid.
- chemical , adverse effects : Immunosuppressive Agents, Mycophenolic Acid.
- chemically induced : Graft Rejection.
- methods : Kidney Transplantation.
- chemical , therapeutic use : Immunosuppressive Agents, Mycophenolic Acid.
- Adult, Age Factors, Aged, Humans, Middle Aged, Models, Biological, ROC Curve.
Abstract
This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35 mg h/L in the first days to 41 mg h/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.
DOI: 10.1016/j.phrs.2013.03.009
PubMed: 23557931
Affiliations:
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Le Meur</name></author><author><name sortKey="Premaud, A" sort="Premaud, A" uniqKey="Premaud A" first="A" last="Prémaud">A. Prémaud</name></author><author><name sortKey="Woillard, J B" sort="Woillard, J B" uniqKey="Woillard J" first="J B" last="Woillard">J B Woillard</name></author><author><name sortKey="Rerolle, J P" sort="Rerolle, J P" uniqKey="Rerolle J" first="J P" last="Rérolle">J P Rérolle</name></author><author><name sortKey="Marquet, P" sort="Marquet, P" uniqKey="Marquet P" first="P" last="Marquet">P. Marquet</name></author><author><name sortKey="Rousseau, A" sort="Rousseau, A" uniqKey="Rousseau A" first="A" last="Rousseau">A. Rousseau</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="doi">10.1016/j.phrs.2013.03.009</idno><idno type="RBID">pubmed:23557931</idno><idno type="pmid">23557931</idno><idno type="wicri:Area/PubMed/Corpus">000230</idno><idno type="wicri:Area/PubMed/Curation">000230</idno><idno type="wicri:Area/PubMed/Checkpoint">000217</idno><idno type="wicri:Area/Ncbi/Merge">000A68</idno><idno type="wicri:Area/Ncbi/Curation">000A68</idno><idno type="wicri:Area/Ncbi/Checkpoint">000A68</idno><idno type="wicri:Area/Main/Merge">000573</idno><idno type="wicri:Area/Main/Curation">000580</idno><idno type="wicri:Area/Main/Exploration">000580</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.</title><author><name sortKey="Daher Abdi, Z" sort="Daher Abdi, Z" uniqKey="Daher Abdi Z" first="Z" last="Daher Abdi">Z. Daher Abdi</name><affiliation wicri:level="1"><nlm:affiliation>Inserm, UMR-S850, Limoges, F-87025 France.</nlm:affiliation><country wicri:rule="zip">France</country><wicri:regionArea>F-87025 France</wicri:regionArea></affiliation></author><author><name sortKey="Essig, M" sort="Essig, M" uniqKey="Essig M" first="M" last="Essig">M. Essig</name></author><author><name sortKey="Rizopoulos, D" sort="Rizopoulos, D" uniqKey="Rizopoulos D" first="D" last="Rizopoulos">D. Rizopoulos</name></author><author><name sortKey="Le Meur, Y" sort="Le Meur, Y" uniqKey="Le Meur Y" first="Y" last="Le Meur">Y. Le Meur</name></author><author><name sortKey="Premaud, A" sort="Premaud, A" uniqKey="Premaud A" first="A" last="Prémaud">A. Prémaud</name></author><author><name sortKey="Woillard, J B" sort="Woillard, J B" uniqKey="Woillard J" first="J B" last="Woillard">J B Woillard</name></author><author><name sortKey="Rerolle, J P" sort="Rerolle, J P" uniqKey="Rerolle J" first="J P" last="Rérolle">J P Rérolle</name></author><author><name sortKey="Marquet, P" sort="Marquet, P" uniqKey="Marquet P" first="P" last="Marquet">P. Marquet</name></author><author><name sortKey="Rousseau, A" sort="Rousseau, A" uniqKey="Rousseau A" first="A" last="Rousseau">A. Rousseau</name></author></analytic><series><title level="j">Pharmacological research</title><idno type="e-ISSN">1096-1186</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Graft Rejection (chemically induced)</term><term>Humans</term><term>Immunosuppressive Agents (administration & dosage)</term><term>Immunosuppressive Agents (adverse effects)</term><term>Immunosuppressive Agents (therapeutic use)</term><term>Kidney Transplantation (methods)</term><term>Middle Aged</term><term>Models, Biological</term><term>Mycophenolic Acid (administration & dosage)</term><term>Mycophenolic Acid (adverse effects)</term><term>Mycophenolic Acid (therapeutic use)</term><term>ROC Curve</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Immunosuppressive Agents</term><term>Mycophenolic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Immunosuppressive Agents</term><term>Mycophenolic Acid</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Graft Rejection</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Kidney Transplantation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Immunosuppressive Agents</term><term>Mycophenolic Acid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Humans</term><term>Middle Aged</term><term>Models, Biological</term><term>ROC Curve</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35 mg h/L in the first days to 41 mg h/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Essig, M" sort="Essig, M" uniqKey="Essig M" first="M" last="Essig">M. Essig</name><name sortKey="Le Meur, Y" sort="Le Meur, Y" uniqKey="Le Meur Y" first="Y" last="Le Meur">Y. Le Meur</name><name sortKey="Marquet, P" sort="Marquet, P" uniqKey="Marquet P" first="P" last="Marquet">P. Marquet</name><name sortKey="Premaud, A" sort="Premaud, A" uniqKey="Premaud A" first="A" last="Prémaud">A. Prémaud</name><name sortKey="Rerolle, J P" sort="Rerolle, J P" uniqKey="Rerolle J" first="J P" last="Rérolle">J P Rérolle</name><name sortKey="Rizopoulos, D" sort="Rizopoulos, D" uniqKey="Rizopoulos D" first="D" last="Rizopoulos">D. Rizopoulos</name><name sortKey="Rousseau, A" sort="Rousseau, A" uniqKey="Rousseau A" first="A" last="Rousseau">A. Rousseau</name><name sortKey="Woillard, J B" sort="Woillard, J B" uniqKey="Woillard J" first="J B" last="Woillard">J B Woillard</name></noCountry><country name="France"><noRegion><name sortKey="Daher Abdi, Z" sort="Daher Abdi, Z" uniqKey="Daher Abdi Z" first="Z" last="Daher Abdi">Z. Daher Abdi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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