Evidence that nephrocalcin and urine inhibit nucleation of calcium oxalate monohydrate crystals

Human urine, and nephrocalcin (NC), a glycoprotein of probable kidney cell origin, greatly reduce consumption of calcium and oxalate from metastably supersaturated solutions seeded with calcium oxalate crystals, a phenomenon usually referred to as inhibition of crystal growth. We seeded metastably supersaturated calcium oxalate solutions with calcium oxalate monohydrate crystals under conditions of ion clamping to maintain constant composition and measured ion consumption from pump delivery rates. Consumption rates increased continuously with time as if the solutions were autocatalytic. After incubation, the seeds were covered with innumerable crystallites, which were also free and numerous in the solution, reflecting self-nucleation. The addition of 20% whole, dialyzed urine, or purified NC reduced ion consumption rates markedly, and the only crystals observed at the end of incubation were the large original seeds. Crystals precoated with concentrated dialyzed urine or NC also showed reduced ion consumption. Urine and NC from patients with nephrolithiasis inhibited nucleation less than normal controls. Self-nucleation seems to be the preferred response in sparsely seeded, ion-clamped, supersaturated solutions, such as exist in the nephron. Urine and NC suppress self-nucleation in vitro by adsorbing to the surface of calcium oxalate crystals.