MP46-19 IDENTIFICATION OF A POTENTIAL BIOMARKER FOR STENT-INDUCED URETERAL DYSFUNCTION

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP46)1 Apr 2020MP46-19 IDENTIFICATION OF A POTENTIAL BIOMARKER FOR STENT-INDUCED URETERAL DYSFUNCTION Kymora Scotland*, Zi-ao Huang, Lu Wang, David Chen, Ben Chew, and Dirk Lange Kymora Scotland*Kymora Scotland* More articles by this author , Zi-ao HuangZi-ao Huang More articles by this author , Lu WangLu Wang More articles by this author , David ChenDavid Chen More articles by this author , Ben ChewBen Chew More articles by this author , and Dirk LangeDirk Lange More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000901.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ureteral stenting can cause symptoms including pain and discomfort in more than 80% of patients. We propose that this pain may be partly due to dysfunctional ureteral peristalsis. Previous work suggested a role for dilation-induced smooth muscle dysfunction in mediating aperistalsis as well as the Gli family of proteins and erythropoietin in regulating contractility. We sought to further investigate specific mechanisms induced by dilation of the ureter and whether they are alleviated via erythropoietin in a porcine model. METHODS: Pigs were stented for set time periods and evaluated for extent and timing of hydronephrosis, ureteral dilation, and rate of peristalsis. Tissue inflammation was graded by a blinded pathologist. RNA and protein expression analyses were used to identify potential biomarkers for ureteral dysfunction. Ureteral function was assessed via quantification of SM contractile forces. Capillary-electrophoresis mass spectrometry was performed in novel metabolomics experiments to quantify inflammatory markers. RESULTS: Stent placement triggers severe ureteral dilation, moderate hydronephrosis and aperistalsis within 48 hours. Stents resulted in inflammatory changes including increased COX-2 expression, a marker of stretch- induced inflammation. Metabolomics experiments showed PGE2, a COX-2 metabolite, expression to be 50% higher after stenting (p< 0.05). Indwelling stents led to increased Gli1, clusterin alpha (kidney injury marker), and collagen 4A2 (marker of fibrotic change) expression in stented ureters versus controls. Erythropoietin did not improve peristalsis or contraction force but did decrease non-purposeful spasming seen exclusively in stented ureters. CONCLUSIONS: We developed a novel assay for quantifying inflammatory markers following stent placement and identified PGE2 as a biomarker for inflammation-induced ureteral dysfunction. COX-2 expression suggests that stents cause stretch induced inflammation of the ureter. Kidney injury and fibrotic change occur after stent placement, leading to Gli family activation and repair processes. Prophylactic erythropoietin may regulate ureteral stabilization in stretch induced spasming following stent placement. Future work will assess the degree and duration of stent-induced injury on ureteral tissue and function. Source of Funding: DC: Natural Science and Engineering Research Council of Canada, DL: independent investigator grant by Boston Scientific. ZH: Mitacs Accelerate PhD Fellowship sponsored by Lipont Pharmaceuticals. KS: Urology Care Foundation Raju Thomas Research Scholar Award and Boston Scientific © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e681-e681 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kymora Scotland* More articles by this author Zi-ao Huang More articles by this author Lu Wang More articles by this author David Chen More articles by this author Ben Chew More articles by this author Dirk Lange More articles by this author Expand All Advertisement PDF downloadLoading ...