Urinary Proteome Enables Noninvasive Differentiation of Ureteropelvic Junction Obstruction from Vesicoureteral Reflux.

PURPOSE: Currently, invasive diagnostic studies are needed to determine the underlying pathology of urinary tract dilation. In this study, we demonstrate that the urinary proteome can be used to differentiate between ureteropelvic junction obstruction and vesicoureteral reflux, which are the 2 most common diagnoses underlying congenital urinary tract dilation. These markers may have the potential to differentiate between obstructive and nonobstructive causes of urinary tract dilation.

MATERIALS AND

METHODS

From a prospectively maintained urinary biorepository in which urine samples from the bladder were collected through catheterization just before surgical intervention, urinary proteins of 2 clinical cohorts of ureteropelvic junction obstruction (n = 102) and vesicoureteral reflux (n = 122) were analyzed by mass spectrometry. After quantitation of protein expression, a panel of predictive proteins was identified, and predictive models were generated (through logistic regression and bootstrap and decision tree analysis). Gene ontology and network analysis were performed using the Ingenuity Pathways Analysis software.

RESULTS

A total of 878 proteins present in all subjects were quantified. 125 proteins were differentially expressed with an absolute fold change > 1.3. Both the feature selection through logistic regression and bootstrap (area under the curve [AUC] 0.98 accuracy 93%) and decision tree (AUC 0.91, accuracy 86%) models demonstrated good classification performance. Pathways analysis of the differentially expressed proteins provided insight into the different biological processes that occur in the 2 groups.

CONCLUSIONS

This study demonstrates differing expression of select urinary proteins between patients with ureteropelvic junction obstruction and vesicoureteral reflux. There is potential for the urinary proteome to be leveraged as a noninvasive method to distinguish between obstructive and nonobstructive causes of congenital urinary dilation.