title: Ultrastructural investigation of crystal deposits in Npt2a knockout mice: are they similar to human Randall's plaques?
abstract: OBJECTIVE
  Idiopathic Ca oxalate stones may develop with attachment to renal interstitial Ca phosphate deposits (Randall's plaques). Sodium phosphate cotransporter (Npt2a) null mice have hypercalciuria and hyperphosphaturia, and produce tubular and interstitial Ca phosphate deposits. To determine whether this mouse is suitable for Randall's plaque investigations we chronologically studied Ca phosphate deposit sites, structure and composition.
  
  
  METHODS
  The kidneys of Npt2a null mice 2 days to 1 year old were examined by light, scanning and transmission electron microscopy. Electron diffraction and energy dispersive x-ray microanalyses were done to determine mineral composition.
  
  
  RESULTS
  Poorly crystalline, biological apatite deposits were seen in collecting duct lumina. Deposits consisted of aggregates approximately 5 μm in diameter appearing as microspheres of concentrically organized needle or plate-like, matrix rich crystals. Epithelium/crystal interfaces were filled with membrane bound vesicles. Some tubules were completely occluded by crystals and occasionally lost the epithelium while crystals moved into the interstitium.
  
  
  CONCLUSIONS
  Ca phosphate crystals formed in the tubular lumina and were organized as microspheres. The aggregation of Ca phosphate crystals produced nuclei, which grew by adding crystals at the periphery. They eventually became large enough to occlude the tubular lumina and obliterate the tubular epithelium, leading to the relocation of microliths into the interstitium. The pathogenesis of interstitial deposits in Npt2a null mice appears different from that proposed for Randall's plaques. Since Npt2a null mice purge the renal crystal deposits, these mice may serve as a model in which to investigate the elimination of crystal deposits in children and adults with nephrocalcinosis.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, Center for the Study of Lithiasis, University of Florida, Gainesville, Florida 32610-0275, USA. khan@pathology.ufl.edu
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Canales
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000378:metabolism*; D003460:Crystallization; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics
chemical_list: D002130:Calcium Phosphates; C493555:Slc34a1 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa