Modulation of Calcium-Oxalate-Monohydrate Crystallization Kinetics in Vitro
Urinary and model compounds were tested in a seeded-crystal growth system in which the effects of additives on the solubility, the growth, and the agglomeration of calcium-oxalate-monohydrate (COM) crystals are measured separately (1). Heparin (0.05–10 μM), chondroitin sulfate (0.1–10 μM), pentosanpolysulfate (1–100 μM),, pyrophosphate (1–100 μM),, citrate (0.05–2.5 mM), magnesium (0.5–10 mM), and phosphate (0.3–30 mM) were tested. The solubility of COM crystals was increased strongly by citrate and magnesium. The crystal growth was inhibited by all compounds tested. However, the high-molecular-weight compounds were the strongest inhibitors at low concentrations already. In contrast, inhibition of crystal agglomeration was achieved only by the low-molecular-weight compounds, and citrate was the most potent inhibitor at concentrations likely to be found in normal urine. The high-molecular-weight substances, despite their strong effect on growth, had no effect on agglomeration. When heparin and citrate were tested together, crystal-growth inhibition was exerted mainly by heparin, while agglomeration was inhibited exclusively by citrate. A combination of citrate with various concentrations of magnesium or various calcium/oxalate ratios, showed that the inhibitory effect of citrate on agglomeration can be modulated by the concentrations of magnesium and calcium present, the active form of citrate probably being its complex with magnesium or calcium.