454 IDENTIFICATION OF POTENTIAL URINARY BIOMARKERS OF CLINICALLY SIGNIFICANT URETEROPELVIC JUNCTION OBSTRUCTION

Abstract

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Kidney & Ureter1 Apr 2012454 IDENTIFICATION OF POTENTIAL URINARY BIOMARKERS OF CLINICALLY SIGNIFICANT URETEROPELVIC JUNCTION OBSTRUCTION John W. Froehlich, Andrew C. Briscoe, Hanno Steen, and Richard S. Lee John W. FroehlichJohn W. Froehlich Boston, MA More articles by this author , Andrew C. BriscoeAndrew C. Briscoe Boston, MA More articles by this author , Hanno SteenHanno Steen Boston, MA More articles by this author , and Richard S. LeeRichard S. Lee Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.522AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Identifying clinically significant kidney obstruction (UPJO) from non-significant hydronephrosis remains difficult. While excellent surgical treatment of UPJO exists, better non-invasive diagnostic tests are needed. In this work, a thorough proteomic analysis of pediatric urine from the obstructed kidney, the normal contralateral kidney, and healthy controls identifies several putative biomarkers which may aid in patient stratification. METHODS Samples were obtained from age- and sex-matched controls, and UPJO patients undergoing pyeloplasty. UPJO urine from both the obstructed kidney (HUK) and the bladder (HUB) representing the contralateral normal kidney was obtained. Samples were processed by a spin-filter based protocol. Proteins were isolated and quantified and equal amounts were digested with trypsin. Peptides were isobarically labeled, mixed and separated by isoelectric focusing. Mass spectrometry was performed on an Orbitrap XL. Peptides were filtered to ensure a 1% false discovery rate, and ANOVA was performed, with a Benjamini-Hochberg multiple testing correction. RESULTS In total, the analysis identified 1114 proteins, and quantified 865 genes. Using strict fold change and statistical cutoffs, 76 proteins were identified as putative biomarkers. Notably, 24 proteins involved with oxidative stress were significantly enriched or depleted in UPJO. Interestingly, 3 proteins with antioxidant protective effects were significantly upregulated in HUK during obstruction, but conversely downregulated in HUB (bladder) possibly indicating a different role in the compensatory mechanism of the contralateral kidney. Several distinct antioxidant defense proteins were significantly upregulated in HUK (up to 18 fold) indicating an increased antioxidant protective role. Interestingly, in HUB, other oxidative stress proteins were downregulated, implying a potential compensatory change in the contralateral kidney. This may be caused by an increase in angiogenesis in the contralateral kidney. CONCLUSIONS Using modern proteomic techniques, isotopic labeling, and stringent statistical cutoffs, 76 UPJO biomarkers were identified. These include several proteins associated with oxidative stress response, angiogenesis and cell-cell adhesion. Notably, quantitative profiles of the obstructed and contralateral kidney were generated independently, reflecting unique proteomic changes in the two kidneys. Future early validation studies are needed to focus the potential biomarker panel. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e185-e186 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information John W. Froehlich Boston, MA More articles by this author Andrew C. Briscoe Boston, MA More articles by this author Hanno Steen Boston, MA More articles by this author Richard S. Lee Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...