Mp63-15 Urinary Stone Disease Development in Apoe -/- Mice Associated With Tubular Basal Membrane Deposits

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-15 URINARY STONE DISEASE DEVELOPMENT IN APOE-/- MICE ASSOCIATED WITH TUBULAR BASAL MEMBRANE DEPOSITS Aaron W. Miller, Jose Agudelo, Mangesh Suryavanshi, Thien Dang, Sromona Mukherjee, and Junchul Shin Aaron W. MillerAaron W. Miller , Jose AgudeloJose Agudelo , Mangesh SuryavanshiMangesh Suryavanshi , Thien DangThien Dang , Sromona MukherjeeSromona Mukherjee , and Junchul ShinJunchul Shin View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Idiopathic calcium oxalate (CaOx) urinary stone disease (USD) is associated with the development of interstitial plaques. Some mouse models with ablation of selected genes can develop the formation of interstitial crystals after long term manipulation. We conducted an oxalate diet trial in the pro-atherogenic Apoe-/- mice to evaluate USD phenotype in this mouse model. METHODS: We conducted an experiment with 56 Apoe-/- mice housed in a barrier facility, 4 animals per cage, under 3 concentrations of oxalate, 2%, 3% and 0% control group for 8-weeks. At the end of the trial, animals were necropsied and phenotyped for USD and atherosclerosis. One kidney was paraffin embedded and stained for CaOx quantification, and one kidney from each group was used for transmission electron microscopy (TEM) to evaluate renal tubular ultrastructure. One kidney from each group was also collected for micro-CT characterization. Atherosclerotic plaques were measured through sequential sectioning of brachiocephalic artery (BCA). Serum was also collected for analysis of lipids, renal function, and oxalate content. RESULTS: Micro-CT conducted on kidneys post necropsy shows the presence of calcifications in the collecting system, as well as pelvis dilation in animals under 3% oxalate diet. Kidneys from animals under 3% oxalate diet stained with Alizarin R show clear findings of obstructive uropathy and crystal nephropathies, like tubular dilation, intratubular crystals, and interstitial orange-red complex compatible with calcium phosphate infiltrates. Renal calcification surface area was significantly larger in animals under 3% oxalate diet (p>0.01). In the same group, TEM images show proximal tubules with intratubular crystals and thin tubules with subepithelial spherulitic deposits in the basal membrane. BCA samples in animals under 3% oxalate diet shows the presence of intima vacuolization as the first stages of atherosclerotic plaque development compared to animals under basal diet. CONCLUSIONS: Our findings of intratubular and interstitial calcifications, as well as subepithelial tubular deposits support the hypothesis that the Apoe-/- can be a feasible model for the study of idiopathic CaOx stone development, with the advantage of phenotype development in a shorter period of time compared to established mouse models. Download PPT Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1037 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Aaron W. Miller More articles by this author Jose Agudelo More articles by this author Mangesh Suryavanshi More articles by this author Thien Dang More articles by this author Sromona Mukherjee More articles by this author Junchul Shin More articles by this author Expand All Advertisement PDF downloadLoading ...