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Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease

David M. Good, Petra Zürbig  Correspondence email, Àngel Argilés, Hartwig W. Bauer, Georg Behrens, Joshua J. Coon, Mohammed Dakna, Stéphane Decramer, Christian Delles, Anna F. Dominiczak, Jochen H. H. Ehrich, Frank Eitner, Danilo Fliser, Moritz Frommberger, Arnold Ganser, Mark A. Girolami, Igor Golovko, Wilfried Gwinner, Marion Haubitz, Stefan Herget-Rosenthal, Joachim Jankowski, Holger Jahn, George Jerums, Bruce A. Julian, Markus Kellmann, Volker Kliem, Walter Kolch, Andrzej S. Krolewski, Mario Luppi, Ziad Massy, Michael Melter, Christian Neusüss, Jan Novak, Karlheinz Peter, Kasper Rossing, Harald Rupprecht, Joost P. Schanstra, Eric Schiffer, Jens-Uwe Stolzenburg, Lise Tarnow, Dan Theodorescu, Visith Thongboonkerd, Raymond Vanholder, Eva M. Weissinger, Harald Mischak and Philippe Schmitt-Kopplin
Molecular & Cellular Proteomics November 1, 2010, First published on July 8, 2010, 9 (11) 2424-2437; https://doi.org/10.1074/mcp.M110.001917
David M. Good
From the Departments of aChemistry and
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Petra Zürbig
cMosaiques Diagnostics GmbH, 30625 Hannover, Germany,
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  • For correspondence: zuerbig@mosaiques-diagnostics.com
Àngel Argilés
fRD Néphrologie, 34090 Montpellier, France,
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Hartwig W. Bauer
gLudwig Maximilians University Munich, 80539 Munich, Germany,
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Georg Behrens
Departments of hClinical Immunology,
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Joshua J. Coon
From the Departments of aChemistry and iBiomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706,
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Mohammed Dakna
cMosaiques Diagnostics GmbH, 30625 Hannover, Germany,
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Stéphane Decramer
jU858/I2MR, Renal and Cardiac Remodeling, INSERM, 31432 Toulouse, France, kPediatric Nephrology Unit, Hopital des Enfants, Centre Hospitalier Universitaire de Toulouse, 31059 Toulouse, France,
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Christian Delles
lBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK,
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Anna F. Dominiczak
lBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK,
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Jochen H. H. Ehrich
nChildren's Hospital, Hannover Medical School, 30625 Hannover, Germany,
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Frank Eitner
oDepartment of Nephrology and Clinical Immunology, RWTH University Hospital, 52074 Aachen, Germany,
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Danilo Fliser
pDepartment of Internal Medicine IV, Saarland University Hospital, 66421 Homburg/Saar, Germany,
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Moritz Frommberger
rInstitute of Ecological Chemistry, Helmholtz Center Munich-German Research Center for Environmental Health, 85764 Neuherberg, Germany,
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Arnold Ganser
sHematology, Hemostasis, Oncology, and Stem Cell Transplantation, and
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Mark A. Girolami
tDepartment of Computing Science, University of Glasgow, Glasgow G12 8QQ, United Kingdom,
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Igor Golovko
cMosaiques Diagnostics GmbH, 30625 Hannover, Germany,
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Wilfried Gwinner
uNephrology and
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Marion Haubitz
uNephrology and
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Stefan Herget-Rosenthal
vDepartment of Medicine, Red Cross Hospital, 28199 Bremen, Germany,
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Joachim Jankowski
wNephrology Department, Charité Hospital, 12200 Berlin, Germany,
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Holger Jahn
yDepartment of Psychiatry, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany,
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George Jerums
zDepartment of Medicine, Austin Health and Northern Health, University of Melbourne, Heidelberg, Victoria 3081, Australia,
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Bruce A. Julian
aaDepartments of Microbiology and Medicine, University of Alabama, Birmingham, Alabama 35294,
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Markus Kellmann
bbThermo Fisher Scientific, 28199 Bremen, Germany,
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Volker Kliem
ccDepartment of Nephrology, Transplantation Centre, Lower Saxony Centre for Nephrology, 34346 Hannoversch Münden, Germany,
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Walter Kolch
ddSystems Biology Ireland, University College Dublin, Dublin 4, United Kingdom,
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Andrzej S. Krolewski
ffSection on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts 02215, ggDepartment of Medicine, Harvard Medical School, Boston, Massachusetts 02215,
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Mario Luppi
hhDepartment of Oncology Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, 41100 Modena, Italy,
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Ziad Massy
iiDepartments of Clinical Pharmacology and Nephrology, INSERM, ERI-12, and Amiens University Hospital, Université de Picardie Jules Verne, 80054 Amiens, France,
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Michael Melter
jjChildren's Hospital, University of Regensburg, 93053 Regensburg, Germany,
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Christian Neusüss
kkDepartment of Analytical Chemistry, University of Aalen, 73430 Aalen, Germany,
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Jan Novak
aaDepartments of Microbiology and Medicine, University of Alabama, Birmingham, Alabama 35294,
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Karlheinz Peter
llDepartment of Atherothrombosis and Vascular, Baker Heart Research Institute, Melbourne, Victoria 8008, Australia,
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Kasper Rossing
mmSteno Diabetes Centre, 2820 Gentofte, Denmark,
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Harald Rupprecht
nnDepartment of Nephrology, Clinical Centre Bayreuth, 95444 Bayreuth, Germany,
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Joost P. Schanstra
jU858/I2MR, Renal and Cardiac Remodeling, INSERM, 31432 Toulouse, France,
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Eric Schiffer
cMosaiques Diagnostics GmbH, 30625 Hannover, Germany,
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Jens-Uwe Stolzenburg
ppDepartment of Urology, University of Leipzig, 04103 Leipzig, Germany,
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Lise Tarnow
mmSteno Diabetes Centre, 2820 Gentofte, Denmark,
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Dan Theodorescu
rrDepartment of Urology, University of Virginia, Charlottesville, Virginia 22908,
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Visith Thongboonkerd
ttFaculty of Medicine at Siriraj Hospital and Center for Research in Complex Systems Sciences, Mahidol University, Bangkok 10700, Thailand, and
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Raymond Vanholder
uuDepartment of Internal Medicine, University Hospital Ghent, 9000 Ghent, Belgium
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Eva M. Weissinger
sHematology, Hemostasis, Oncology, and Stem Cell Transplantation, and
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Harald Mischak
cMosaiques Diagnostics GmbH, 30625 Hannover, Germany, lBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK,
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Philippe Schmitt-Kopplin
rInstitute of Ecological Chemistry, Helmholtz Center Munich-German Research Center for Environmental Health, 85764 Neuherberg, Germany,
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Abstract

Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.

Footnotes

  • ↵d On behalf of the European Kidney and Urine Proteomics consortium.

  • ↵m Supported by InGenious HyperCare Grant LSHM-CT-2006-037093 and British Heart Foundation Grant RG/02/012.

  • ↵q On behalf of the European Uremic Toxin consortium.

  • ↵x Supported by Federal Ministry of Education and Research Grant NGFN/01GR0807.

  • ↵ee Supported by the Biotechnology and Biological Sciences Research Council and Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration in Proteomic Technology (IRColl) Grant Radical Solutions for Researching the Proteome (RASOR) and Wellcome Trust Joint Infrastructure Fund Proteomics Grant 29240.

  • ↵oo Supported by INSERM, the “Direction Régional de la Recherche Clinique” (Centre Hospitalier Universitaire de Toulouse, France) under the Interface program and by the Fondation pour la Recherche Médicale.

  • ↵qq Supported by European Union Prevention of Diabetic Complications (PREDICTIONS) Grant LSHM-CT-2005-018733.

  • ↵vv Supported by European Union PREDICTIONS Grant LSHM-CT-2005-018733 and by InGenious HyperCare Grant LSHM-CT- 2006-037093.

  • ↵ww Supported by European Union to Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment (sysKID) Grant HEALTH-F2-2009-241544.

  • ↵* This work was supported, in whole or in part, by National Institutes of Health Grants DK067638 (to A. S. K.); Grants DK075868, DK078244, DK061525, DK080301, and DK082753 (to B. A. J. and J. N.); and Biotechnology Training Program Predoctoral Fellowship Grant 5T32GM08349 (to D. M. G.). This work was also supported by Eurotransbio Grant ETB-2006-016 to the Urosysteomics consortium (www.urosysteomics.com) (to E. S. and H. M.), Lower Saxony Ministry of Economy Grant 203.19-32329-5-461 (to A. G., E. M. W., and H. M.), and the Joslin Diabetes Center. H. Mischak is founder and co-owner of Mosaiques Diagnostics GmbH, which developed the CE-MS technology and the MosaiquesVisu software. P. Zürbig, M. Dakna, Igor Golovko, and Eric Schiffer are employees of Mosaiques Diagnostics GmbH.

  • ↵Embedded Image This article contains supplemental Tables I–III and figures showing mass spectra.

  • Received June 11, 2010.
  • Revision received June 30, 2010.
  • © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease
David M. Good, Petra Zürbig, Àngel Argilés, Hartwig W. Bauer, Georg Behrens, Joshua J. Coon, Mohammed Dakna, Stéphane Decramer, Christian Delles, Anna F. Dominiczak, Jochen H. H. Ehrich, Frank Eitner, Danilo Fliser, Moritz Frommberger, Arnold Ganser, Mark A. Girolami, Igor Golovko, Wilfried Gwinner, Marion Haubitz, Stefan Herget-Rosenthal, Joachim Jankowski, Holger Jahn, George Jerums, Bruce A. Julian, Markus Kellmann, Volker Kliem, Walter Kolch, Andrzej S. Krolewski, Mario Luppi, Ziad Massy, Michael Melter, Christian Neusüss, Jan Novak, Karlheinz Peter, Kasper Rossing, Harald Rupprecht, Joost P. Schanstra, Eric Schiffer, Jens-Uwe Stolzenburg, Lise Tarnow, Dan Theodorescu, Visith Thongboonkerd, Raymond Vanholder, Eva M. Weissinger, Harald Mischak, Philippe Schmitt-Kopplin
Molecular & Cellular Proteomics November 1, 2010, First published on July 8, 2010, 9 (11) 2424-2437; DOI: 10.1074/mcp.M110.001917

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Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease
David M. Good, Petra Zürbig, Àngel Argilés, Hartwig W. Bauer, Georg Behrens, Joshua J. Coon, Mohammed Dakna, Stéphane Decramer, Christian Delles, Anna F. Dominiczak, Jochen H. H. Ehrich, Frank Eitner, Danilo Fliser, Moritz Frommberger, Arnold Ganser, Mark A. Girolami, Igor Golovko, Wilfried Gwinner, Marion Haubitz, Stefan Herget-Rosenthal, Joachim Jankowski, Holger Jahn, George Jerums, Bruce A. Julian, Markus Kellmann, Volker Kliem, Walter Kolch, Andrzej S. Krolewski, Mario Luppi, Ziad Massy, Michael Melter, Christian Neusüss, Jan Novak, Karlheinz Peter, Kasper Rossing, Harald Rupprecht, Joost P. Schanstra, Eric Schiffer, Jens-Uwe Stolzenburg, Lise Tarnow, Dan Theodorescu, Visith Thongboonkerd, Raymond Vanholder, Eva M. Weissinger, Harald Mischak, Philippe Schmitt-Kopplin
Molecular & Cellular Proteomics November 1, 2010, First published on July 8, 2010, 9 (11) 2424-2437; DOI: 10.1074/mcp.M110.001917
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Molecular & Cellular Proteomics: 9 (11)
Molecular & Cellular Proteomics
Vol. 9, Issue 11
1 Nov 2010
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