Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
Identifieur interne : 000987 ( Main/Exploration ); précédent : 000986; suivant : 000988Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery
Auteurs : Melanie Meersch [Allemagne] ; Christoph Schmidt [Allemagne] ; Hugo Van Aken [Allemagne] ; Sven Martens [Allemagne] ; Jan Rossaint [Allemagne] ; Kai Singbartl [États-Unis] ; Dennis Görlich [Allemagne] ; John A. Kellum [États-Unis] ; Alexander Zarbock [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Aire sous la courbe, Atteinte rénale aigüe (diagnostic), Atteinte rénale aigüe (urine), Atteinte rénale aigüe (étiologie), Complications postopératoires, Courbe ROC, Créatinine (sang), Défaillance cardiaque (), Défaillance cardiaque (urine), Expression des gènes, Femelle, Humains, Inhibiteur tissulaire de métalloprotéinase-2 (génétique), Inhibiteur tissulaire de métalloprotéinase-2 (urine), Marqueurs biologiques (urine), Mâle, Pontage cardiopulmonaire (effets indésirables), Pronostic, Protéines de liaison aux IGF (génétique), Protéines de liaison aux IGF (urine), Sujet âgé, Sujet âgé de 80 ans ou plus.
- MESH :
- diagnostic : Atteinte rénale aigüe.
- effets indésirables : Pontage cardiopulmonaire.
- génétique : Inhibiteur tissulaire de métalloprotéinase-2, Protéines de liaison aux IGF.
- sang : Créatinine.
- étiologie : Atteinte rénale aigüe, Défaillance cardiaque.
- urine : Aire sous la courbe, Complications postopératoires, Courbe ROC, Défaillance cardiaque, Expression des gènes, Femelle, Humains, Inhibiteur tissulaire de métalloprotéinase-2, Marqueurs biologiques, Mâle, Pronostic, Protéines de liaison aux IGF, Sujet âgé, Sujet âgé de 80 ans ou plus.
English descriptors
- KwdEn :
- Acute Kidney Injury (diagnosis), Acute Kidney Injury (etiology), Acute Kidney Injury (urine), Aged, Aged, 80 and over, Area Under Curve, Biomarkers (urine), Cardiopulmonary Bypass (adverse effects), Creatinine (blood), Female, Gene Expression, Heart Failure (complications), Heart Failure (surgery), Heart Failure (urine), Humans, Insulin-Like Growth Factor Binding Proteins (genetics), Insulin-Like Growth Factor Binding Proteins (urine), Male, Postoperative Complications, Prognosis, ROC Curve, Tissue Inhibitor of Metalloproteinase-2 (genetics), Tissue Inhibitor of Metalloproteinase-2 (urine).
- MESH :
- chemical , blood : Creatinine.
- chemical , genetics : Insulin-Like Growth Factor Binding Proteins, Tissue Inhibitor of Metalloproteinase-2.
- chemical , urine : Biomarkers, Insulin-Like Growth Factor Binding Proteins, Tissue Inhibitor of Metalloproteinase-2.
- adverse effects : Cardiopulmonary Bypass.
- complications : Heart Failure.
- diagnosis : Acute Kidney Injury.
- etiology : Acute Kidney Injury.
- surgery : Heart Failure.
- urine : Acute Kidney Injury, Heart Failure.
- Aged, Aged, 80 and over, Area Under Curve, Female, Gene Expression, Humans, Male, Postoperative Complications, Prognosis, ROC Curve.
Abstract
Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients.
We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge.
26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1–3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery.
Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery.
Url:
DOI: 10.1371/journal.pone.0093460
PubMed: 24675717
PubMed Central: 3968141
Affiliations:
- Allemagne, États-Unis
- District de Münster, Pennsylvanie, Rhénanie-du-Nord-Westphalie
- Münster, Pittsburgh
- Université de Pittsburgh
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Le document en format XML
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type="main">Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery</title><author><name sortKey="Meersch, Melanie" sort="Meersch, Melanie" uniqKey="Meersch M" first="Melanie" last="Meersch">Melanie Meersch</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Schmidt, Christoph" sort="Schmidt, Christoph" uniqKey="Schmidt C" first="Christoph" last="Schmidt">Christoph Schmidt</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Van Aken, Hugo" sort="Van Aken, Hugo" uniqKey="Van Aken H" first="Hugo" last="Van Aken">Hugo Van Aken</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Martens, Sven" sort="Martens, Sven" uniqKey="Martens S" first="Sven" last="Martens">Sven Martens</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Cardiac Surgery, University of Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Cardiac Surgery, University of Münster</wicri:regionArea><wicri:noRegion>University of Münster</wicri:noRegion><wicri:noRegion>University of Münster</wicri:noRegion><wicri:noRegion>University of Münster</wicri:noRegion></affiliation></author><author><name sortKey="Rossaint, Jan" sort="Rossaint, Jan" uniqKey="Rossaint J" first="Jan" last="Rossaint">Jan Rossaint</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Singbartl, Kai" sort="Singbartl, Kai" uniqKey="Singbartl K" first="Kai" last="Singbartl">Kai Singbartl</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Gorlich, Dennis" sort="Gorlich, Dennis" uniqKey="Gorlich D" first="Dennis" last="Görlich">Dennis Görlich</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biostatistics and Clinical Research, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Kellum, John A" sort="Kellum, John A" uniqKey="Kellum J" first="John A." last="Kellum">John A. Kellum</name><affiliation wicri:level="4"><nlm:aff id="aff5"><addr-line>Center for Critical Care Nephrology, CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Critical Care Nephrology, CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Zarbock, Alexander" sort="Zarbock, Alexander" uniqKey="Zarbock A" first="Alexander" last="Zarbock">Alexander Zarbock</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute Kidney Injury (diagnosis)</term><term>Acute Kidney Injury (etiology)</term><term>Acute Kidney Injury (urine)</term><term>Aged</term><term>Aged, 80 and over</term><term>Area Under Curve</term><term>Biomarkers (urine)</term><term>Cardiopulmonary Bypass (adverse effects)</term><term>Creatinine (blood)</term><term>Female</term><term>Gene Expression</term><term>Heart Failure (complications)</term><term>Heart Failure (surgery)</term><term>Heart Failure (urine)</term><term>Humans</term><term>Insulin-Like Growth Factor Binding Proteins (genetics)</term><term>Insulin-Like Growth Factor Binding Proteins (urine)</term><term>Male</term><term>Postoperative Complications</term><term>Prognosis</term><term>ROC Curve</term><term>Tissue Inhibitor of Metalloproteinase-2 (genetics)</term><term>Tissue Inhibitor of Metalloproteinase-2 (urine)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Aire sous la courbe</term><term>Atteinte rénale aigüe (diagnostic)</term><term>Atteinte rénale aigüe (urine)</term><term>Atteinte rénale aigüe (étiologie)</term><term>Complications postopératoires</term><term>Courbe ROC</term><term>Créatinine (sang)</term><term>Défaillance cardiaque ()</term><term>Défaillance cardiaque (urine)</term><term>Expression des gènes</term><term>Femelle</term><term>Humains</term><term>Inhibiteur tissulaire de métalloprotéinase-2 (génétique)</term><term>Inhibiteur tissulaire de métalloprotéinase-2 (urine)</term><term>Marqueurs biologiques (urine)</term><term>Mâle</term><term>Pontage cardiopulmonaire (effets indésirables)</term><term>Pronostic</term><term>Protéines de liaison aux IGF (génétique)</term><term>Protéines de liaison aux IGF (urine)</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Creatinine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Insulin-Like Growth Factor Binding Proteins</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="urine" xml:lang="en"><term>Biomarkers</term><term>Insulin-Like Growth Factor Binding Proteins</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Cardiopulmonary Bypass</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Heart Failure</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Acute Kidney Injury</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Atteinte rénale aigüe</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Pontage cardiopulmonaire</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Acute Kidney Injury</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Inhibiteur tissulaire de métalloprotéinase-2</term><term>Protéines de liaison aux IGF</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Créatinine</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Heart Failure</term></keywords><keywords scheme="MESH" qualifier="urine" xml:lang="en"><term>Acute Kidney Injury</term><term>Heart Failure</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Atteinte rénale aigüe</term><term>Défaillance cardiaque</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Area Under Curve</term><term>Female</term><term>Gene Expression</term><term>Humans</term><term>Male</term><term>Postoperative Complications</term><term>Prognosis</term><term>ROC Curve</term></keywords><keywords scheme="MESH" qualifier="urine" xml:lang="fr"><term>Aire sous la courbe</term><term>Complications postopératoires</term><term>Courbe ROC</term><term>Défaillance cardiaque</term><term>Expression des gènes</term><term>Femelle</term><term>Humains</term><term>Inhibiteur tissulaire de métalloprotéinase-2</term><term>Marqueurs biologiques</term><term>Mâle</term><term>Pronostic</term><term>Protéines de liaison aux IGF</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients.</p></sec><sec><title>Methods</title><p>We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge.</p></sec><sec><title>Results</title><p>26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1–3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery.</p></sec><sec><title>Conclusions</title><p>Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery.</p></sec><sec><title>Clinical Trial Registration Information:</title><p><ext-link ext-link-type="uri" xlink:href="http://www.germanctr.de/">www.germanctr.de/</ext-link>, DRKS-ID: DRKS00005062</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wijeysundera, Dn" uniqKey="Wijeysundera D">DN Wijeysundera</name></author><author><name sortKey="Karkouti, K" uniqKey="Karkouti K">K Karkouti</name></author><author><name sortKey="Dupuis, Jy" uniqKey="Dupuis J">JY Dupuis</name></author><author><name sortKey="Rao, V" uniqKey="Rao V">V Rao</name></author><author><name sortKey="Chan, Ct" uniqKey="Chan C">CT 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Pittsburgh</li></orgName></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Meersch, Melanie" sort="Meersch, Melanie" uniqKey="Meersch M" first="Melanie" last="Meersch">Melanie Meersch</name></region><name sortKey="Gorlich, Dennis" sort="Gorlich, Dennis" uniqKey="Gorlich D" first="Dennis" last="Görlich">Dennis Görlich</name><name sortKey="Martens, Sven" sort="Martens, Sven" uniqKey="Martens S" first="Sven" last="Martens">Sven Martens</name><name sortKey="Rossaint, Jan" sort="Rossaint, Jan" uniqKey="Rossaint J" first="Jan" last="Rossaint">Jan Rossaint</name><name sortKey="Schmidt, Christoph" sort="Schmidt, Christoph" uniqKey="Schmidt C" first="Christoph" last="Schmidt">Christoph Schmidt</name><name sortKey="Van Aken, Hugo" sort="Van Aken, Hugo" uniqKey="Van Aken H" first="Hugo" last="Van Aken">Hugo Van Aken</name><name sortKey="Zarbock, Alexander" sort="Zarbock, Alexander" uniqKey="Zarbock A" first="Alexander" last="Zarbock">Alexander Zarbock</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Singbartl, Kai" sort="Singbartl, Kai" uniqKey="Singbartl K" first="Kai" last="Singbartl">Kai Singbartl</name></region><name sortKey="Kellum, John A" sort="Kellum, John A" uniqKey="Kellum J" first="John A." last="Kellum">John A. 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