Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease.
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.
Good
David M
DM
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Zürbig
Petra
P
Argilés
Angel
A
Bauer
Hartwig W
HW
Behrens
Georg
G
Coon
Joshua J
JJ
Dakna
Mohammed
M
Decramer
Stéphane
S
Delles
Christian
C
Dominiczak
Anna F
AF
Ehrich
Jochen H H
JH
Eitner
Frank
F
Fliser
Danilo
D
Frommberger
Moritz
M
Ganser
Arnold
A
Girolami
Mark A
MA
Golovko
Igor
I
Gwinner
Wilfried
W
Haubitz
Marion
M
Herget-Rosenthal
Stefan
S
Jankowski
Joachim
J
Jahn
Holger
H
Jerums
George
G
Julian
Bruce A
BA
Kellmann
Markus
M
Kliem
Volker
V
Kolch
Walter
W
Krolewski
Andrzej S
AS
Luppi
Mario
M
Massy
Ziad
Z
Melter
Michael
M
Neusüss
Christian
C
Novak
Jan
J
Peter
Karlheinz
K
Rossing
Kasper
K
Rupprecht
Harald
H
Schanstra
Joost P
JP
Schiffer
Eric
E
Stolzenburg
Jens-Uwe
JU
Tarnow
Lise
L
Theodorescu
Dan
D
Thongboonkerd
Visith
V
Vanholder
Raymond
R
Weissinger
Eva M
EM
Mischak
Harald
H
Schmitt-Kopplin
Philippe
P
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D016208:Databases, Factual; D019075:Electrophoresis, Capillary / Q000379:methods; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000652:urine; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D055815:Young Adult
D015415:Biomarkers; D010455:Peptides