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

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. 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. 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. 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.