Cell-crystal interactions and kidney stone formation

Background: Renal tubular fluid in the distal nephron is supersaturated wit h calcium and oxalate ions that nucleate to form crystals of calcium oxalat e monohydrate (COM), the most common crystal in renal stones. How these nas cent crystals are retained in the nephron to form calculi in certain indivi duals is not known. Methods: The results of experiments conducted in this a nd other laboratories that employ cell culture model systems to explore ren al epithelial cell-urinary crystal interactions are described. Results: COM crystals rapidly adhere to anionic sites on the surface of cultured renal epithelial cells, but this process can be inhibited, if specific urinary an ions such as glycosaminoglycans, uropontin, nephrocalcin, or citrate are av ailable to coat the crystalline surface. Therefore, competition for the cry stal surface between soluble anions in tubular fluid and anions on the apic al cell surface could determine whether or not a crystal binds to the cell. A similar paradigm describes adhesion of calcium phosphate (hydroxyapatite ) crystals, also a common constituent of human stones. Once bound, COM and hydroxyapatite crystals are quickly internalized by renal cells; reorganiza tion of the cytoskeleton, alterations in gene expression, and initiation of proliferation may then ensue. Each of these cellular events appears to be regulated by a different set of extracellular factors. Over several weeks i n culture, renal cells (BSC-1 line) dissolve internalized crystals, althoug h once a cell binds a crystal, additional crystals are more likely to bind, possibly forming a positive feedback loop that results in kidney stone for mation. Conclusions: Increased knowledge about the cell-crystal interaction , including identification of molecules in tubular fluid and on the cell su rface that modulate the process, and understanding its mechanism of action appear critical for explaining the pathogenesis of nephrolithiasis.