Natural urinary macromolecular inhibitors: attenuation of inhibitory activity by urate salts

The interaction between naturally occurring urinary macromolecular inhibitors of calcium oxalate nucleation and crystal growth and the various urate salts was explored in vitro. The fraction of macromolecules chosen for the study was the one which was previously shown to have a potent inhibitor activity against calcium oxalate nucleation and one which gave a satisfactory yield. As little as 0.025 mg/ml of this fraction (Y-b) was found to inhibit calcium oxalate nucleation by nearly 50% and crystal growth by 31%. Prior incubation of the solution containing Y-b with increasing crystal surface areas (1.1 to 26.2 mm2/ml) of monosodium urate (NaU), monopotassium urate (KU), or uric acid (UA) attenuated the inhibitory action of the Y-b fraction for both nucleation and crystal growth of calcium oxalate. The most prominent effect was elicited by NaU at surface areas as small as 1.1 mm2/ml. Potassium urate and UA were without significant effects until surface areas of 13.1 and 2.6 mm2/ml, respectively, were achieved. These results support an important pathogenetic role for urates (particularly NaU) in the development of hyperuricosuric calcium urolithiasis.