Exosomal proteomic analysis reveals changes in the urinary proteome of rats with unilateral ureteral obstruction

Abstract

Congenital urinary tract obstruction (UTO) is a commonly noted disorder with the potential to cause permanent loss of renal function. Due to the possibility of spontaneous resolution, postnatal management strategies require lengthy and invasive surveillance methods to monitor the status of renal function and severity of obstruction. Here, a quantitative proteome analysis of urinary exosomes from weanling rats with surgically introduced UTO identifies a number of candidate biomarkers with the potential to improve diagnostic and prognostic methods for this disease. Using gel-assisted digestion coupled to liquid chromatography/tandem mass spectrometry (LC–MS/MS), 318 proteins were identified. Relative protein quantitation by spectral counting showed 190 proteins with significant changes in abundance due to either partial or complete obstruction. Numerous proteins identified here have been shown to be similarly altered in abundance in other renal diseases that cause tubule apoptosis and interstitial fibrosis. Extrapolating the role of the proteins showing quantifiable changes in abundance here from other forms of renal disease suggests they have potential for clinical applicability as biomarkers of congenital UTO. Included in the list of identified proteins are markers of apoptosis, oxidative stress, fibrosis, inflammation, and tubular cell damage, which are commonly associated with UTO. This study therefore provides a number of candidate biomarkers that, following validation in children experiencing UTO, have the potential to improve postnatal management of this disease.