Further evidence that brushite plays a regulatory role in renal stone formation was provided by the identification of brushite as the first precipitate that appears in supersaturated urine by spontaneous precipitation. Calcium chloride was added to induce supersaturation in urine specimens from twelve subjects with and twelve subjects without nephrolithiasis.The first precipitate in all specimens with pH below 6.9 was identified as brushite by x-ray diffraction and shown to have a calcium-phosphorus ratio of approximately 1.0.The activity product of [Ca'+i X [HP0421-necessary to produce a precipitate ranged from 2.2 to 3.5 times the solubility product of brushite, but the range and mean were the same for both groups of subjects.The activity product of [Cal+] X [HPO42-] in the supernatant (after spontaneous precipitation) was not significantly different from that obtained after incubation of the same urine specimen with synthetic brushite.These results provide conclusive evidence that brushite constitutes the solid phase formed by spontaneous precipitation from acidic urine supersaturated with respect to calcium and phosphorus; they suggest that the nidus for calcium-containing renal stones is brushite as well.Physicochemical factors controlling the formation of calciumcontaining renal stones cannot be understood until the initial precipitate is identified. When this precipitate forms on an organic matrix or is added to a preexisting stone, it is composed of brushite (CaHPO4 * 2H20), and is deposited when the activity product of [Ca2+] X [HP042-] in the urine exceeds the activity product (K.,) of brushite (1-4).In earlier studies, a ratio of the solubility product of the actual urinary K.,, for brushite to that of urine with an added excess of solid brushite allowed quantitative calculation of the tendency for stone growth and corrected for any error in the calculation of activities for Ca2+ and HP042-(2).These results were used to explain growth of stones in some patients with hypercalciuria and some with urine persistently alkaline as a result of therapy with alkali or of urinary-tract infection by urea splitters. In the first group, the urine is supersaturated with respect to brushite, primarily because of an abnormally high concentration of Ca2+ ions. Stone formation is prevented when the concentration of urinary calcium (and thus the activity product for brushite) is lowered by the feeding of nonabsorbable chelators of calcium, or, in patients with hyperparathyroidism, by its surgical correction. In the second group, the urine is supersaturated primarily because of an abnormally high concentration of HP042-ions; stone formation is prevented when the urinary concentration of HP042-(and the activity product for brushite) is lowered by avoidance of alkali or by elimination of infection.The conclusion that brushite is indeed the initial nidus that forms from urine onto an organic matrix was supported by the demonstration that the activity product for brushite controls nidation on an artificial "matrix" ...