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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. Key words: exosomes, proteomics, biomarkers, urinary tract obstruction. L'obstruction congenitale des voies urinaires est un trouble frequemment observe qui peut entrainer la perte de la fonction renale. Etant donne la possibilite de resolution spontanee, les strategies de prise en charge postnatale requierent des methodes de surveillance longues et invasives pour que l'etat de la fonction renale et la gravite de l'obstruction puissent etre suivis. Dans le present article, une analyse quantitative du proteome des exosomes urinaires de ratons sevres sur lesquels une obstruction des voies urinaire a ete pratiquee par chirurgie a permis de relever un certain nombre de biomarqueurs potentiels qui pourraient permettre d'ameliorer les methodes de diagnostic et de pronostic de cette maladie. A l'aide de la digestion sur gel couplee a la Chromatographie liquide et la spectrometrie de masse en tandem (LC-MS/MS), nous avons repere 318 proteines. La quantification relative des proteines par comptage spectral a permis d'en relever 190 dont le changement en abondance etait attribuable a une obstruction soit partielle ou complete. Des modifications similaires de l'abondance de nombreuses proteines parmi celles que nous avons trouvees ont ete observees dans le contexte d'autres maladies renales qui causent l'apoptose tabulaire et la fibrose interstitielle. En extrapolant le rôle des proteines qui ont montre dans les presents travaux des modifications quantifiables de leur abondance a partir de celui qu'elles jouent dans d'autres formes de maladie renale, on peut supposer que ces proteines pourraient trouver des applications cliniques comme biomarqueurs de l'obstruction congenitale des voies urinaires. Parmi les proteines repertoriees, on compte des marqueurs de l'apoptose, du stress oxydant, de la fibrose, de l'inflammation et des lesions des cellules tubulaires, qui sont communement associes a l'obstruction des voies urinaires. Cette etude propose donc un certain nombre de biomarqueurs potentiels qui, apres validation chez des enfants presentant une obstruction des voies urinaires, pourraient ameliorer la prise en charge postnatale de cette maladie. [Traduit par la Redaction] Mots-cles : exosomes, proteomique, biomarqueurs, obstruction des voies urinaires., Introduction Congenital urinary tract obstruction (UTO) is a common cause of prenatally diagnosed hydronephrosis, (1-3) and remains a leading cause of renal functional loss in children. (3,4) Hydronephrosis often resolves [...]

Congenital anomalies of the kidney and urinary tract (CAKUT) are diagnosed in approximately 3-6 per 1000 live births and represent a spectrum of urologic conditions impacting the kidneys, ureter, bladder, and urethra.1 Although both are considered under the classification of CAKUT, there is no known unifying pathophysiologic mechanism for ureteroceles and posterior urethral valves with only 1 case report noted in the literature. Herein we report the only documented case of a patient with CAKUT related to posterior urethral valves, ureterocele, and multicystic dysplastic kidney. [ABSTRACT FROM AUTHOR]

Introduction: Practitioners have anecdotally hinted at a possible association between gastroesophageal reflux disease (GERD) and vesicoureteral reflux (VUR). We sought to identify an association in diagnosis between GERD and VUR using a population-based dataset in a welldefined geographic area covered by a single-payer healthcare system. Methods: A retrospective review of individuals aged 0-16 years registered in the Nova Scotia Medical Service Insurance database from January 1997 to December 2012 was completed. Presence of GERD and VUR were ascertained based on billing codes. The baseline prevalence of GERD and VUR was calculated for this population for the same time period. Proportions of VUR patients with and without GERD were compared. The risk of being diagnosed with VUR in patients with GERD controlling for sex was calculated. Results: Of 404 300 patients identified, 6.6% had a diagnosis of GERD (n=27 092), 0.33% had a diagnosis of VUR (n=1348), and 0.08% were diagnosed with both (n=327). Among patients with VUR, the prevalence of GERD was 24.3% compared to 6.6% in patients without VUR (p<0.0001). Among patients with GERD, the prevalence of VUR was 1.2% compared to 0.27% in patients without (p<0.0001). The risk of being diagnosed with VUR was higher in the presence of GERD (odds ratio [OR] 4.49; 95% confidence interval [CI] 3.96-5.09; p<0.0001), irrespective of sex. Conclusions: The odds of being diagnosed with VUR is more than 4.5 times higher in an individual with GERD. The clinical significance of this association remains to be explored [ABSTRACT FROM AUTHOR]

Inherent to the biomarker discovery process is a comparative analysis of physiological states. It is therefore critical that the proteome detection protocol does not bias the analysis. With urine, the sediment portion, obtained upon thawing frozen urine, is routinely discarded prior to proteome analysis. However, our results demonstrate that such a practice inadvertently induces bias, having significant implications in the biomarker discovery process. We present the first proteome investigation of human urinary sediments, identifying 60 proteins in this phase by MS. Many sediment proteins were also detected in the urinary supernatant, indicating that several proteins partition between the two phases. This partitioning is dependant on the pH of the sample, as well as the degree of sample agitation. As a consequence of discarding the sediment portion of urine, the concentration of potential candidate biomarkers in the supernatant phase will be altered or, in other instances, may be completely removed from the sample. To minimize this, the pH of all samples should first be normalized, and the samples vigorously vortexed prior to discarding the sediments. For more comprehensive biomarker investigations, we suggest that urinary sediments be analyzed along with the supernatant proteins., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)