Urinary Proteome Enables Non-invasive 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 utilized to differentiate between ureteropelvic junction obstruction and vesicoureteral reflux, which are the two most common diagnoses underlying congenital urinary tract dilation. These markers may have the potential to differentiate between obstructive and non-obstructive causes of urinary tract dilation. MATERIALS AND METHODS: From a prospectively maintained urinary biorepository in which urine samples from the bladder were collected via catheterization just prior to surgical intervention, urinary proteins of two clinical cohorts of ureteropelvic junction obstruction (n=102) and vesicoureteral reflux (n=122) were analyzed by mass spectrometry. Following quantitation of protein expression, a panel of predictive proteins was identified, and predictive models were generated (via logistic regression and bootstrap, and decision tree analysis). Gene ontology and network analysis was 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 via logistic regression and bootstrap (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 two 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 non-invasive method to distinguish between obstructive and nonobstructive causes of congenital urinary dilation.