title: Apatite in kidney stones is a molecular composite with glycosaminoglycans and proteins: evidence from nuclear magnetic resonance spectroscopy, and relevance to Randall's plaque, pathogenesis and prophylaxis.
abstract: OBJECTIVE
  We characterized the biomacromolecular composition of phosphatic urinary stones using solid state nuclear magnetic resonance spectroscopy. We identified possible parallels between the nature of the organic matrix-mineral interface in stones and that in other mineralized tissue using nuclear magnetic resonance spectroscopy rotational echo double resonance.
  
  
  METHODS
  We analyzed 28 phosphatic (apatite and mixed apatite-struvite) surgically removed stones by nuclear magnetic resonance spectroscopy using (31)P, (13)C and a 9.4 Tesla magnetic field. Ten samples had sufficient signal from biomacromolecular organic material to characterize the mineral/organic interface by (13)C{(31)P} rotational echo double resonance.
  
  
  RESULTS
  Biomacromolecular organic material was most abundant in phosphatic stones in which apatite predominated. Nuclear magnetic resonance spectroscopy detected variable proportions of protein, glycosaminoglycan, lipid and carbonate. Rotational echo double resonance revealed strong interaction between mineral and glycosaminoglycan molecules, and to a lesser extent protein molecules, on the sub-nm length scale, implying that glycosaminoglycan and protein are composited into or onto the mineral lattice by strong physicochemical interactions. Carbonate ions substituted into apatite crystal lattices also showed the expected strong (13)C{(31)P} rotational echo double resonance effects. Conversely when present, lipid, calcium oxalate hydrates and uric acid showed no rotational echo double resonance effects, proving that they exist as deposits or crystals distinct from phosphatic mineral/biomacromolecular composites.
  
  
  CONCLUSIONS
  The intimate coexistence of biomacromolecules, especially glycosaminoglycan, with apatite in phosphatic stones supports the notion that they may have a key role in stone pathogenesis. The underlying intermolecular relationships may reflect those governing the formation of Randall's plaque in nascent stones.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: David G
authors.initials: DG
authors.lastname: Reid
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Jackson
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Duer
authors.forename: Allen L
authors.initials: AL
authors.lastname: Rodgers
mesh_terms: D001031:Apatites / Q000737:chemistry*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000503:physiopathology / Q000517:prevention & control; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011322:Primary Prevention; D011506:Proteins / Q000378:metabolism*; D012494:Sampling Studies; D012720:Severity of Illness Index
chemical_list: D001031:Apatites; D006025:Glycosaminoglycans; D011506:Proteins