Influence of Supersaturation Level on the Efficacy of Crystallization Inhibitors

This in vitro study examined the influence of supersaturation level on the efficacy of different inhibitors in preventing the crystallization of calcium oxalate, uric acid, and cystine. Kinetic–turbidimetric assays were used to determine the induction time of crystallization (ti) in the absence and presence of different inhibitors. For calcium oxalate, the inhibitory effects of citrate, hydroxycitrate, tartronate, and phytate decreased significantly as the Ca2+ concentration increased from 220 mg/L to 240 mg/L. The polyhydroxycarboxylic compounds (citrate, hydroxycitrate, tartronate) can form complexes with calcium ions, decreasing overall supersaturation. Even though phytate also forms complexes with calcium, its urinary concentration is much lower than that of calcium, so the decrease in supersaturation can be considered negligible. For uric acid, theobromine and two of its metabolites (3-methylxanthine and 7-methylxanthine) inhibited the formation of these crystals. For each compound, the efficacy of inhibition decreased as the supersaturation of uric acid increased. For cystine, the inhibitory effect of N-acetylcysteine was lower at pH 4.5 and 5.0 than at pH 6.0. These studies of the crystallization of calcium oxalate, uric acid, and cystine showed that the efficacy of crystallization inhibitors decreased as the level of supersaturation increased. The results demonstrate that, in patients prone to kidney stone formation, the effectiveness of crystallization inhibitors can be improved by reducing the supersaturation of the specific stone-forming compound.