Inhibitors of stone formation

Urine contains substances that inhibit the nucleation, growth, aggregation, and cell attachment of crystals. These may function to protect the kidney against the possibility of pathological calcification in tubular fluid and urine, which are generally supersaturated with respect to calcium salts, thereby preventing stone formation. Effects on calcium oxalate are the best studied, and most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans. Inhibitory proteins found in urine include nephrocalcin, Tamm-Horsfall protein, uropontin, crystal matrix protein (F1 prothrombin fragment), and uronic acid-rich protein (bikunin). Most of the molecules are anionic, with many acidic amino acid residues, frequently contain post-translational modifications such as phosphorylation and glycosylation, and appear to exert their effects by binding to calcium oxalate surface. The specific structural motifs that favor crystal binding and inhibition are not yet known. A number of the proteins are made by renal epithelial cells, whereas others gain access to the urine by glomerular filtration. In a number of cases, abnormalities of protein structure or function have been found in stone formers. It is not yet known what proportion of stone formers have an abnormality of inhibitor function.