Isolation of calcium oxalate crystal growth inhibitor from rat kidney and urine.

Glycoproteins that slow the growth rate of calcium oxalate monohydrate crystals were purified from rat kidney homogenate and urine by selective heat denaturation (for rat kidney homogenate), DEAE-cellulose column chromatography, and gel permeation column chromatography. Both kidney and urine inhibitors were glycoproteins with an apparent mol wt of 1.4 X 10(4), as determined by high-performance liquid chromatography. They contained gamma-carboxyglutamic acid and a high percentage of aspartic acid and glutamic acid but had few aromatic amino acid residues. Both inhibitors contained fucose, mannose, glucose, galactose, glucosamine, galactosamine, and N-acetylneuraminic acid but no glucuronic acid. Kinetic studies suggest that purified inhibitors bind to calcium oxalate monohydrate seed crystals according to a Langmuir adsorption isotherm with similar dissociation constants of 14 X 10(-8)M for rat urine inhibitor and 8.7 X 10(-8) M for rat kidney inhibitor. The isolation of similar glycoproteins from kidney and urine suggests that urinary crystal growth inhibitor may be produced in the kidneys.