2051 DEVELOPMENT OF INTERSTITIAL CALCIUM PHOSPHATE DEPOSITS IN SODIUM PHOSPHATE CO-TRANSPORTER (NPT2A) NULL MICE

Abstract

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112051 DEVELOPMENT OF INTERSTITIAL CALCIUM PHOSPHATE DEPOSITS IN SODIUM PHOSPHATE CO-TRANSPORTER (NPT2A) NULL MICE Benjamin Canales and Saeed Khan Benjamin CanalesBenjamin Canales Gainesville, FL More articles by this author and Saeed KhanSaeed Khan Gainesville, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2282AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The mechanisms involved in pathogenesis and growth of renal interstitial calcium phosphate (CaP) deposits (Randall's plaque, RP) are unknown. Sodium phosphate co-transporter knock-out mice (NPT2a) are hypercalciuric, hyperphosphaturic, and produce tubular and interstitial CaP deposits. To determine if this mouse is a suitable model for RP investigations, we chronologically studied the location, structure, and composition of mineral deposits in NPT2a mice. METHODS Kidneys of NPT2a null mice aged 2 days–14 months were examined by light microscopy, scanning (SEM) and transmission electron microscopy (TEM). Electron diffraction and energy dispersive x-ray microanalyses (EDAX) were performed to determine mineral composition, and osteopontin (OPN) stain was used for immunohistochemistry. RESULTS Amorphous biological apatite deposits, confirmed by EDAX, were identified within tubular and collecting duct lumens of all kidneys studied (Figure). By TEM, organic matrix was concentrically arranged around a central nidus of 5 micron diameter microspheres aggregating into organized, plate-like crystals. Interface between epithelium and crystals were filled with membrane bound vesicles. Some tubules, completely occluded by crystals, lost their epithelium and architecture. These areas stained strongly positive for osteopontin, and the remaining deposits appeared to be interstitial, adjacent to blood vessels, peritubular cells, and collagen fibers. CONCLUSIONS In NPT2a null mice, thin plate-like CaP crystals form within tubular lumens, organize as microspheres, and aggregate to produce a nucleus. By addition of crystal onto the periphery, deposits eventually grow large enough to occlude tubular lumen and obliterate tubular epithelium, leading to relocation of microliths into the interstitium. Thus, the CaP deposits of NPT2a null mice appear to have different origins than those of human Randall's plaque. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e821 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Canales Gainesville, FL More articles by this author Saeed Khan Gainesville, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...