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URINARY LEVELS OF PROXIMAL TUBULE PROTEINS ARE SIGNIFICANTLY
ELEVATED IN THE SETTING OF URETEROPELVIC JUNCTION OBSTRUCTION AND
MAY REPRESENT NOVEL BIOMARKERS
Miriam HAREL
1
, Claire GERBER
2
, Miranda LYNCH
2
, Linda SHAPIRO
2
and Fernando FERRER
1
1) University of Connecticut Health Center/Connecticut Children's Medical Center, Department of Vascular
Biology/Urology, Farmington/hartford, USA - 2) University of Connecticut Health Center, Department of Vascular
Biology, Farmington, USA
PURPOSE
Urinary biomarkers have the potential to aid in the diagnosis and management of ureteropelvic junction obstruction
(UPJO). Destruction and shedding of proximal tubule brush border proteins occurs early in obstructive uropathy. Thus,
we hypothesized that urinary levels of the tubular proteins CD10, CD13, and CD26 would be elevated in the setting of
UPJO and could represent novel biomarkers.
MATERIAL AND METHODS
A murine model of complete unilateral ureteral obstruction was utilized, and urine was harvested from the obstructed
renal pelvis and bladder after seven and ten days. Voided urine was also obtained from 12 patients with UPJO and 12
controls. Murine urinary protein levels were determined using western blotting, and human urine was analyzed with
sandwich ELISA. Protein levels were normalized to urinary creatinine. Human samples were also tested for the published
candidate biomarkers KIM-1 and NGAL.
RESULTS
In the murine model, levels of CD10, CD13, and CD26 were increased in urine from the obstructed renal pelvis
compared to bladder urine produced by the unligated kidney at both time points tested. These proteins were also
significantly increased in urine samples from patients with UPJO compared to normal controls. No statistical differences
were observed in the levels of KIM-1 and NGAL between control and experimental groups.
CONCLUSIONS
Urinary levels of CD10, CD13, and CD26 are significantly elevated in the setting of UPJO and may represent novel
biomarkers. Further studies are necessary to validate these findings and to determine the correlation of these urinary
protein levels with renal damage.