1969 ULTRA-STRUCTURAL STUDY OF RENAL PAPILLARY CALCINOSIS IN TAMM-HORSFALL PROTEIN KNOCKOUT MICE: RELATION TO RANDALL'S PLAQUES IN HUMANS (2010)

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20101969 ULTRA-STRUCTURAL STUDY OF RENAL PAPILLARY CALCINOSIS IN TAMM-HORSFALL PROTEIN KNOCKOUT MICE: RELATION TO RANDALL'S PLAQUES IN HUMANS Yan Liu, Lan Mo, David Goldfarb, Andrew Evan, Fengxia Liang, Saeed Khan, John Lieske, and Xue-Ru Wu Yan LiuYan Liu New York, NY More articles by this author , Lan MoLan Mo New York, NY More articles by this author , David GoldfarbDavid Goldfarb New York, NY More articles by this author , Andrew EvanAndrew Evan Indianapolis, IN More articles by this author , Fengxia LiangFengxia Liang New York, NY More articles by this author , Saeed KhanSaeed Khan Gainesville, FL More articles by this author , John LieskeJohn Lieske Rochester, MN More articles by this author , and Xue-Ru WuXue-Ru Wu New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1979AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tamm-Horsfall protein (THP), the most abundant protein in human urine, has long been suspected to be a modulator of urinary mineral crystallization, but whether it acts as a facilitator or an inhibitor remained controversial. We recently showed that genetically engineered mice lacking THP were prone to developing spontaneous, intra-renal calcium deposits. The present study was undertaken to elucidate the ultrastructural characteristics and chemical composition of these deposits and to determine their relationship to human Randall's plaques. METHODS Ten to 15 month-old mice in which THP gene was functionally ablated and wild-type controls were sacrificed and their kidneys processed for transmission electron microscopy (TEM). Alternatively, the kidneys were processed for von Kossa staining and light microscopy (LM) for crystal identification followed by Fourier transform infrared microspectroscopy (ì-FTIR) for chemical composition determination. RESULTS Intra-renal deposits in THP-null mice were confined to the papillary region. The majority of the crystals were located interstitially, although intra-tubular crystals were also present. Interstitial crystals were mostly seen in widened basement membrane zone of the collecting tubules and thin limbs. TEM of the interstitial crystals showed onion-ring or tree-trunk appearance, with electron dense materials interspersed by less-dense materials presumably consisting of proteinaceous substances. The crystals were not accompanied by inflammatory cell infiltration. Micro-FTIR revealed that the interstitial crystals contained mainly calcium phosphate in the form of hydroxyapatite, with a small amount of calcium carbonate. Intra-tubular crystals were less organized, varied in size and shape, were mixed with amorphous materials and cell debris, and did not exhibit onion-ring structure. CONCLUSIONS The location, ultra-structure, chemical composition and lack of associated inflammation of the interstitial crystals in THP-null mice strongly resemble those of “Randall's plaques”, often found in human kidneys bearing idiopathic stones. Our data suggest THP deficiency as an important contributor to human kidney stone formation. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e764-e765 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yan Liu New York, NY More articles by this author Lan Mo New York, NY More articles by this author David Goldfarb New York, NY More articles by this author Andrew Evan Indianapolis, IN More articles by this author Fengxia Liang New York, NY More articles by this author Saeed Khan Gainesville, FL More articles by this author John Lieske Rochester, MN More articles by this author Xue-Ru Wu New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...