Candidate urinary biomarker discovery in ureteropelvic junction obstruction: a proteomic approach.
OBJECTIVE
Ureteropelvic junction obstruction may either worsen and require surgery, improve or remain stable. It may take upward of 3 years for the natural history to unfold. Urinary proteome analysis using capillary electrophoresis mass spectrometry has been shown to differentiate between normal infants and those with ureteropelvic junction obstruction. We sought to confirm these findings using liquid chromatography/nano-spray mass spectrometry to examine the urinary proteome in patients with unilateral grade IV ureteropelvic junction obstruction compared to age matched healthy infants.


METHODS
Urine specimens were obtained from 21 healthy infants with normal maternal/fetal ultrasound and 25 infants with grade IV unilateral ureteropelvic junction obstruction. Specimens were prepared using standard methods and subjected to liquid chromatography/tandem mass spectrometry analysis. Normalized data were annotated using the IPA(R) knowledge platform.


RESULTS
There were 31 proteins significantly different in their level of abundance at 1 to 6 months, and 18 at 7 to 12 months compared to age matched controls. These proteins clustered into major functional networks. All of the biomarkers previously reported in clinical studies of ureteropelvic junction obstruction were observed with the notable exception of transforming growth factor-beta1.


CONCLUSIONS
These results confirm the presence of significant differences in the urinary proteome in unilateral ureteropelvic junction obstruction compared to age matched normal individuals. This study adds new information about levels of abundance of specific proteins and peptides in ureteropelvic junction obstruction, which may allow for better classification of disease subgroups and help to establish improved indications for the early selection of surgical candidates based on urinary protein biomarkers.
Mesrobian
Hrair-George O
HG
Department of Urology, Medical College and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA. hmesrobi@mcw.edu
Mitchell
Michael E
ME
See
William A
WA
Halligan
Brian D
BD
Carlson
Brian E
BE
Greene
Andrew S
AS
Wakim
Bassam T
BT
D015415:Biomarkers / Q000652:urine; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007682:Kidney Pelvis; D008297:Male; D010865:Pilot Projects; D020543:Proteome; D014517:Ureteral Obstruction / Q000652:urine*
D015415:Biomarkers; D020543:Proteome