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Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.

Identifieur interne : 002B23 ( PubMed/Corpus ); précédent : 002B22; suivant : 002B24

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.

Auteurs : Joost P. Schanstra ; Petra Zürbig ; Alaa Alkhalaf ; Angel Argiles ; Stephan J L. Bakker ; Joachim Beige ; Henk J G. Bilo ; Christos Chatzikyrkou ; Mohammed Dakna ; Jesse Dawson ; Christian Delles ; Hermann Haller ; Marion Haubitz ; Holger Husi ; Joachim Jankowski ; George Jerums ; Nanne Kleefstra ; Tatiana Kuznetsova ; David M. Maahs ; Jan Menne ; William Mullen ; Alberto Ortiz ; Frederik Persson ; Peter Rossing ; Piero Ruggenenti ; Ivan Rychlik ; Andreas L. Serra ; Justyna Siwy ; Janet Snell-Bergeon ; Goce Spasovski ; Jan A. Staessen ; Antonia Vlahou ; Harald Mischak ; Raymond Vanholder

Source :

RBID : pubmed:25589610

English descriptors

Abstract

Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.

DOI: 10.1681/ASN.2014050423
PubMed: 25589610

Links to Exploration step

pubmed:25589610

Le document en format XML

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<nlm:affiliation>Institute of Cardiovascular and Metabolic Disease, French Institute of Health and Medical Research U1048, Toulouse, France; Paul Sabatier University (Toulouse III), Toulouse, France;</nlm:affiliation>
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<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands;</nlm:affiliation>
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<name sortKey="Argiles, Angel" sort="Argiles, Angel" uniqKey="Argiles A" first="Angel" last="Argiles">Angel Argiles</name>
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<nlm:affiliation>RD Néphrologie, Montpellier, France;</nlm:affiliation>
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<name sortKey="Bakker, Stephan J L" sort="Bakker, Stephan J L" uniqKey="Bakker S" first="Stephan J L" last="Bakker">Stephan J L. Bakker</name>
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<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands;</nlm:affiliation>
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<name sortKey="Beige, Joachim" sort="Beige, Joachim" uniqKey="Beige J" first="Joachim" last="Beige">Joachim Beige</name>
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<nlm:affiliation>KfH Renal Unit, Department Nephrology, Leipzig and Martin-Luther-University, Halle/Wittenberg, Germany;</nlm:affiliation>
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<name sortKey="Bilo, Henk J G" sort="Bilo, Henk J G" uniqKey="Bilo H" first="Henk J G" last="Bilo">Henk J G. Bilo</name>
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<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; Diabetes Centre, Isala Clinics, Zwolle, The Netherlands;</nlm:affiliation>
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<name sortKey="Chatzikyrkou, Christos" sort="Chatzikyrkou, Christos" uniqKey="Chatzikyrkou C" first="Christos" last="Chatzikyrkou">Christos Chatzikyrkou</name>
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<nlm:affiliation>Department of Nephrology and Hypertension, University Hospital of Magdeburg, Magdeburg, Germany;</nlm:affiliation>
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<name sortKey="Dakna, Mohammed" sort="Dakna, Mohammed" uniqKey="Dakna M" first="Mohammed" last="Dakna">Mohammed Dakna</name>
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<nlm:affiliation>mosaiques diagnostics GmbH, Hanover, Germany;</nlm:affiliation>
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<name sortKey="Dawson, Jesse" sort="Dawson, Jesse" uniqKey="Dawson J" first="Jesse" last="Dawson">Jesse Dawson</name>
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<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
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<name sortKey="Delles, Christian" sort="Delles, Christian" uniqKey="Delles C" first="Christian" last="Delles">Christian Delles</name>
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<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
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<name sortKey="Haller, Hermann" sort="Haller, Hermann" uniqKey="Haller H" first="Hermann" last="Haller">Hermann Haller</name>
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<nlm:affiliation>Department of Nephrology and Hypertension, Medical School of Hanover, Hanover, Germany;</nlm:affiliation>
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<name sortKey="Haubitz, Marion" sort="Haubitz, Marion" uniqKey="Haubitz M" first="Marion" last="Haubitz">Marion Haubitz</name>
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<nlm:affiliation>Department of Nephrology, Klinikum Fulda gAG, Fulda, Germany;</nlm:affiliation>
</affiliation>
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<name sortKey="Husi, Holger" sort="Husi, Holger" uniqKey="Husi H" first="Holger" last="Husi">Holger Husi</name>
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<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Jankowski, Joachim" sort="Jankowski, Joachim" uniqKey="Jankowski J" first="Joachim" last="Jankowski">Joachim Jankowski</name>
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<nlm:affiliation>Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany; Department of Internal Medicine IV, Charity Medical University of Berlin, Berlin, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Jerums, George" sort="Jerums, George" uniqKey="Jerums G" first="George" last="Jerums">George Jerums</name>
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<nlm:affiliation>Austin Health, University of Melbourne, Heidelberg, Australia;</nlm:affiliation>
</affiliation>
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<name sortKey="Kleefstra, Nanne" sort="Kleefstra, Nanne" uniqKey="Kleefstra N" first="Nanne" last="Kleefstra">Nanne Kleefstra</name>
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<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; Diabetes Centre, Isala Clinics, Zwolle, The Netherlands;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Kuznetsova, Tatiana" sort="Kuznetsova, Tatiana" uniqKey="Kuznetsova T" first="Tatiana" last="Kuznetsova">Tatiana Kuznetsova</name>
<affiliation>
<nlm:affiliation>Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
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<name sortKey="Maahs, David M" sort="Maahs, David M" uniqKey="Maahs D" first="David M" last="Maahs">David M. Maahs</name>
<affiliation>
<nlm:affiliation>Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Menne, Jan" sort="Menne, Jan" uniqKey="Menne J" first="Jan" last="Menne">Jan Menne</name>
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<nlm:affiliation>Department of Nephrology and Hypertension, Medical School of Hanover, Hanover, Germany;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Mullen, William" sort="Mullen, William" uniqKey="Mullen W" first="William" last="Mullen">William Mullen</name>
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<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Ortiz, Alberto" sort="Ortiz, Alberto" uniqKey="Ortiz A" first="Alberto" last="Ortiz">Alberto Ortiz</name>
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<nlm:affiliation>School of Medicine, Jimenez Diaz Foundation Institute for Health Research, Autonomous University of Madrid, Madrid, Spain;</nlm:affiliation>
</affiliation>
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<name sortKey="Persson, Frederik" sort="Persson, Frederik" uniqKey="Persson F" first="Frederik" last="Persson">Frederik Persson</name>
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<nlm:affiliation>Steno Diabetes Center, Gentofte, Denmark;</nlm:affiliation>
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<name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
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<nlm:affiliation>Steno Diabetes Center, Gentofte, Denmark; Faculty of Health, University of Aarhus, Aarhus, Denmark; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
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<name sortKey="Ruggenenti, Piero" sort="Ruggenenti, Piero" uniqKey="Ruggenenti P" first="Piero" last="Ruggenenti">Piero Ruggenenti</name>
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<nlm:affiliation>Mario Negri Institute of Pharmacology Research, Bergamo, Italy;</nlm:affiliation>
</affiliation>
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<name sortKey="Rychlik, Ivan" sort="Rychlik, Ivan" uniqKey="Rychlik I" first="Ivan" last="Rychlik">Ivan Rychlik</name>
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<nlm:affiliation>Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Serra, Andreas L" sort="Serra, Andreas L" uniqKey="Serra A" first="Andreas L" last="Serra">Andreas L. Serra</name>
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<nlm:affiliation>Division of Nephrology, University Hospital, and Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland;</nlm:affiliation>
</affiliation>
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<name sortKey="Siwy, Justyna" sort="Siwy, Justyna" uniqKey="Siwy J" first="Justyna" last="Siwy">Justyna Siwy</name>
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<nlm:affiliation>mosaiques diagnostics GmbH, Hanover, Germany; Department of Internal Medicine IV, Charity Medical University of Berlin, Berlin, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Snell Bergeon, Janet" sort="Snell Bergeon, Janet" uniqKey="Snell Bergeon J" first="Janet" last="Snell-Bergeon">Janet Snell-Bergeon</name>
<affiliation>
<nlm:affiliation>Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Spasovski, Goce" sort="Spasovski, Goce" uniqKey="Spasovski G" first="Goce" last="Spasovski">Goce Spasovski</name>
<affiliation>
<nlm:affiliation>University Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Staessen, Jan A" sort="Staessen, Jan A" uniqKey="Staessen J" first="Jan A" last="Staessen">Jan A. Staessen</name>
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<nlm:affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Vlahou, Antonia" sort="Vlahou, Antonia" uniqKey="Vlahou A" first="Antonia" last="Vlahou">Antonia Vlahou</name>
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<nlm:affiliation>Division of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece; School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth, United Kingdom; and.</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Mischak, Harald" sort="Mischak, Harald" uniqKey="Mischak H" first="Harald" last="Mischak">Harald Mischak</name>
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<nlm:affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Vanholder, Raymond" sort="Vanholder, Raymond" uniqKey="Vanholder R" first="Raymond" last="Vanholder">Raymond Vanholder</name>
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<nlm:affiliation>Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.</nlm:affiliation>
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<title xml:lang="en">Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.</title>
<author>
<name sortKey="Schanstra, Joost P" sort="Schanstra, Joost P" uniqKey="Schanstra J" first="Joost P" last="Schanstra">Joost P. Schanstra</name>
<affiliation>
<nlm:affiliation>Institute of Cardiovascular and Metabolic Disease, French Institute of Health and Medical Research U1048, Toulouse, France; Paul Sabatier University (Toulouse III), Toulouse, France;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Zurbig, Petra" sort="Zurbig, Petra" uniqKey="Zurbig P" first="Petra" last="Zürbig">Petra Zürbig</name>
<affiliation>
<nlm:affiliation>mosaiques diagnostics GmbH, Hanover, Germany; zuerbig@mosaiques-diagnostics.com.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Alkhalaf, Alaa" sort="Alkhalaf, Alaa" uniqKey="Alkhalaf A" first="Alaa" last="Alkhalaf">Alaa Alkhalaf</name>
<affiliation>
<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Argiles, Angel" sort="Argiles, Angel" uniqKey="Argiles A" first="Angel" last="Argiles">Angel Argiles</name>
<affiliation>
<nlm:affiliation>RD Néphrologie, Montpellier, France;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bakker, Stephan J L" sort="Bakker, Stephan J L" uniqKey="Bakker S" first="Stephan J L" last="Bakker">Stephan J L. Bakker</name>
<affiliation>
<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Beige, Joachim" sort="Beige, Joachim" uniqKey="Beige J" first="Joachim" last="Beige">Joachim Beige</name>
<affiliation>
<nlm:affiliation>KfH Renal Unit, Department Nephrology, Leipzig and Martin-Luther-University, Halle/Wittenberg, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bilo, Henk J G" sort="Bilo, Henk J G" uniqKey="Bilo H" first="Henk J G" last="Bilo">Henk J G. Bilo</name>
<affiliation>
<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; Diabetes Centre, Isala Clinics, Zwolle, The Netherlands;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Chatzikyrkou, Christos" sort="Chatzikyrkou, Christos" uniqKey="Chatzikyrkou C" first="Christos" last="Chatzikyrkou">Christos Chatzikyrkou</name>
<affiliation>
<nlm:affiliation>Department of Nephrology and Hypertension, University Hospital of Magdeburg, Magdeburg, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Dakna, Mohammed" sort="Dakna, Mohammed" uniqKey="Dakna M" first="Mohammed" last="Dakna">Mohammed Dakna</name>
<affiliation>
<nlm:affiliation>mosaiques diagnostics GmbH, Hanover, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Dawson, Jesse" sort="Dawson, Jesse" uniqKey="Dawson J" first="Jesse" last="Dawson">Jesse Dawson</name>
<affiliation>
<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Delles, Christian" sort="Delles, Christian" uniqKey="Delles C" first="Christian" last="Delles">Christian Delles</name>
<affiliation>
<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Haller, Hermann" sort="Haller, Hermann" uniqKey="Haller H" first="Hermann" last="Haller">Hermann Haller</name>
<affiliation>
<nlm:affiliation>Department of Nephrology and Hypertension, Medical School of Hanover, Hanover, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Haubitz, Marion" sort="Haubitz, Marion" uniqKey="Haubitz M" first="Marion" last="Haubitz">Marion Haubitz</name>
<affiliation>
<nlm:affiliation>Department of Nephrology, Klinikum Fulda gAG, Fulda, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Husi, Holger" sort="Husi, Holger" uniqKey="Husi H" first="Holger" last="Husi">Holger Husi</name>
<affiliation>
<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Jankowski, Joachim" sort="Jankowski, Joachim" uniqKey="Jankowski J" first="Joachim" last="Jankowski">Joachim Jankowski</name>
<affiliation>
<nlm:affiliation>Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Aachen, Germany; Department of Internal Medicine IV, Charity Medical University of Berlin, Berlin, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Jerums, George" sort="Jerums, George" uniqKey="Jerums G" first="George" last="Jerums">George Jerums</name>
<affiliation>
<nlm:affiliation>Austin Health, University of Melbourne, Heidelberg, Australia;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kleefstra, Nanne" sort="Kleefstra, Nanne" uniqKey="Kleefstra N" first="Nanne" last="Kleefstra">Nanne Kleefstra</name>
<affiliation>
<nlm:affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; Diabetes Centre, Isala Clinics, Zwolle, The Netherlands;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kuznetsova, Tatiana" sort="Kuznetsova, Tatiana" uniqKey="Kuznetsova T" first="Tatiana" last="Kuznetsova">Tatiana Kuznetsova</name>
<affiliation>
<nlm:affiliation>Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Maahs, David M" sort="Maahs, David M" uniqKey="Maahs D" first="David M" last="Maahs">David M. Maahs</name>
<affiliation>
<nlm:affiliation>Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Menne, Jan" sort="Menne, Jan" uniqKey="Menne J" first="Jan" last="Menne">Jan Menne</name>
<affiliation>
<nlm:affiliation>Department of Nephrology and Hypertension, Medical School of Hanover, Hanover, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Mullen, William" sort="Mullen, William" uniqKey="Mullen W" first="William" last="Mullen">William Mullen</name>
<affiliation>
<nlm:affiliation>BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Ortiz, Alberto" sort="Ortiz, Alberto" uniqKey="Ortiz A" first="Alberto" last="Ortiz">Alberto Ortiz</name>
<affiliation>
<nlm:affiliation>School of Medicine, Jimenez Diaz Foundation Institute for Health Research, Autonomous University of Madrid, Madrid, Spain;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Persson, Frederik" sort="Persson, Frederik" uniqKey="Persson F" first="Frederik" last="Persson">Frederik Persson</name>
<affiliation>
<nlm:affiliation>Steno Diabetes Center, Gentofte, Denmark;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
<affiliation>
<nlm:affiliation>Steno Diabetes Center, Gentofte, Denmark; Faculty of Health, University of Aarhus, Aarhus, Denmark; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Ruggenenti, Piero" sort="Ruggenenti, Piero" uniqKey="Ruggenenti P" first="Piero" last="Ruggenenti">Piero Ruggenenti</name>
<affiliation>
<nlm:affiliation>Mario Negri Institute of Pharmacology Research, Bergamo, Italy;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Rychlik, Ivan" sort="Rychlik, Ivan" uniqKey="Rychlik I" first="Ivan" last="Rychlik">Ivan Rychlik</name>
<affiliation>
<nlm:affiliation>Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Serra, Andreas L" sort="Serra, Andreas L" uniqKey="Serra A" first="Andreas L" last="Serra">Andreas L. Serra</name>
<affiliation>
<nlm:affiliation>Division of Nephrology, University Hospital, and Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Siwy, Justyna" sort="Siwy, Justyna" uniqKey="Siwy J" first="Justyna" last="Siwy">Justyna Siwy</name>
<affiliation>
<nlm:affiliation>mosaiques diagnostics GmbH, Hanover, Germany; Department of Internal Medicine IV, Charity Medical University of Berlin, Berlin, Germany;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Snell Bergeon, Janet" sort="Snell Bergeon, Janet" uniqKey="Snell Bergeon J" first="Janet" last="Snell-Bergeon">Janet Snell-Bergeon</name>
<affiliation>
<nlm:affiliation>Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Spasovski, Goce" sort="Spasovski, Goce" uniqKey="Spasovski G" first="Goce" last="Spasovski">Goce Spasovski</name>
<affiliation>
<nlm:affiliation>University Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Staessen, Jan A" sort="Staessen, Jan A" uniqKey="Staessen J" first="Jan A" last="Staessen">Jan A. Staessen</name>
<affiliation>
<nlm:affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Vlahou, Antonia" sort="Vlahou, Antonia" uniqKey="Vlahou A" first="Antonia" last="Vlahou">Antonia Vlahou</name>
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<nlm:affiliation>Division of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece; School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth, United Kingdom; and.</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Mischak, Harald" sort="Mischak, Harald" uniqKey="Mischak H" first="Harald" last="Mischak">Harald Mischak</name>
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<nlm:affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Vanholder, Raymond" sort="Vanholder, Raymond" uniqKey="Vanholder R" first="Raymond" last="Vanholder">Raymond Vanholder</name>
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<nlm:affiliation>Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.</nlm:affiliation>
</affiliation>
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<title level="j">Journal of the American Society of Nephrology : JASN</title>
<idno type="eISSN">1533-3450</idno>
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<term>Adult</term>
<term>Aged</term>
<term>Biomarkers (urine)</term>
<term>Cohort Studies</term>
<term>Disease Progression</term>
<term>Female</term>
<term>Glomerular Filtration Rate</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Peptides (urine)</term>
<term>Renal Insufficiency, Chronic (urine)</term>
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<term>Biomarkers</term>
<term>Peptides</term>
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<term>Renal Insufficiency, Chronic</term>
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<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Cohort Studies</term>
<term>Disease Progression</term>
<term>Female</term>
<term>Glomerular Filtration Rate</term>
<term>Humans</term>
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<div type="abstract" xml:lang="en">Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.</div>
</front>
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<Year>2015</Year>
<Month>08</Month>
<Day>03</Day>
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<DateCompleted>
<Year>2015</Year>
<Month>11</Month>
<Day>02</Day>
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<Year>2017</Year>
<Month>09</Month>
<Day>22</Day>
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<ISSN IssnType="Electronic">1533-3450</ISSN>
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<Volume>26</Volume>
<Issue>8</Issue>
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<Year>2015</Year>
<Month>Aug</Month>
</PubDate>
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<Title>Journal of the American Society of Nephrology : JASN</Title>
<ISOAbbreviation>J. Am. Soc. Nephrol.</ISOAbbreviation>
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<ArticleTitle>Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.</ArticleTitle>
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<Abstract>
<AbstractText>Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.</AbstractText>
<CopyrightInformation>Copyright © 2015 by the American Society of Nephrology.</CopyrightInformation>
</Abstract>
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<ForeName>Joost P</ForeName>
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<Affiliation>Institute of Cardiovascular and Metabolic Disease, French Institute of Health and Medical Research U1048, Toulouse, France; Paul Sabatier University (Toulouse III), Toulouse, France;</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Zürbig</LastName>
<ForeName>Petra</ForeName>
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<Affiliation>mosaiques diagnostics GmbH, Hanover, Germany; zuerbig@mosaiques-diagnostics.com.</Affiliation>
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<LastName>Alkhalaf</LastName>
<ForeName>Alaa</ForeName>
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<Affiliation>University Medical Center Groningen and University of Groningen, Groningen, The Netherlands;</Affiliation>
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<LastName>Bilo</LastName>
<ForeName>Henk J G</ForeName>
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<LastName>Haubitz</LastName>
<ForeName>Marion</ForeName>
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</AffiliationInfo>
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<ForeName>Nanne</ForeName>
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<LastName>Kuznetsova</LastName>
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<Affiliation>Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</Affiliation>
</AffiliationInfo>
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<LastName>Maahs</LastName>
<ForeName>David M</ForeName>
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<Affiliation>Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado;</Affiliation>
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<LastName>Mullen</LastName>
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<LastName>Ortiz</LastName>
<ForeName>Alberto</ForeName>
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<ForeName>Peter</ForeName>
<Initials>P</Initials>
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<Affiliation>Steno Diabetes Center, Gentofte, Denmark; Faculty of Health, University of Aarhus, Aarhus, Denmark; Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y">
<LastName>Ruggenenti</LastName>
<ForeName>Piero</ForeName>
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<ForeName>Andreas L</ForeName>
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<Affiliation>Division of Nephrology, University Hospital, and Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland;</Affiliation>
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<LastName>Siwy</LastName>
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<Affiliation>mosaiques diagnostics GmbH, Hanover, Germany; Department of Internal Medicine IV, Charity Medical University of Berlin, Berlin, Germany;</Affiliation>
</AffiliationInfo>
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<ForeName>Janet</ForeName>
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<LastName>Spasovski</LastName>
<ForeName>Goce</ForeName>
<Initials>G</Initials>
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</AffiliationInfo>
</Author>
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<LastName>Staessen</LastName>
<ForeName>Jan A</ForeName>
<Initials>JA</Initials>
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<Affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Vlahou</LastName>
<ForeName>Antonia</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Division of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece; School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth, United Kingdom; and.</Affiliation>
</AffiliationInfo>
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<LastName>Mischak</LastName>
<ForeName>Harald</ForeName>
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<Affiliation>Faculty of Health, University of Copenhagen, Copenhagen, Denmark;</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Vanholder</LastName>
<ForeName>Raymond</ForeName>
<Initials>R</Initials>
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<Affiliation>Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.</Affiliation>
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<Agency>European Research Council</Agency>
<Country>International</Country>
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<Grant>
<GrantID>R01 HL113029</GrantID>
<Acronym>HL</Acronym>
<Agency>NHLBI NIH HHS</Agency>
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