Peptide inhibitors of calcium phosphate precipitation in the urine of normal and stone-forming men

Robertson, William; Hambleton, Joan; Hodgkinson, A.

doi:10.1016/0009-8981(69)90262-9

Cited by 21 publications

(6 citation statements)

References 7 publications

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“…If the urine specimens in the nephrolithiasis group lacked inhibitors of nucleation, as has been proposed by some workers (11,12), the formation product ratios from these urine specimens should have been lower than those from the control group. A similar conclusion was reached by Robertson and colleagues (13), and by us, previously, from studies of the calcification of collagen (4).…”

Section: The Formation Product Ratiosupporting

confidence: 85%

Spontaneous Precipitation of Brushite in Urine: Evidence that Brushite Is the Nidus of Renal Stones Originating as Calcium Phosphate

Pak

Eanes

Ruskin

1971

Proc. Natl. Acad. Sci. U.S.A.

102

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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" ...

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Section: The Formation Product Ratiosupporting

confidence: 85%

Spontaneous Precipitation of Brushite in Urine: Evidence that Brushite Is the Nidus of Renal Stones Originating as Calcium Phosphate

Pak

Eanes

Ruskin

1971

Proc. Natl. Acad. Sci. U.S.A.

102

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“…The pattern of collagen calcification by urine specimens of patients with stones was similar to that by specimens from subjects without stones. This observation is consistent with the recent results of Robertson, Hambleton, and Hodgkinson (19), who questioned the absence or reduction of urinary peptides inhibitors as etiologically important in the formation of renal stones.…”

Section: Discussionsupporting

confidence: 93%

Calcification of collagen by urine in vitro: dependence on the degree of saturation of urine with respect to brushite

Pak¹,

Ruskin²

1970

J. Clin. Invest.

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A B S T R A C T A state of supersaturation of urine with respect to brushite is considered to be important in the formation of renal stones composed of calcium phosphate. 56 supersaturated urine specimens and 44 undersaturated specimens were incubated with collagen (Sigma collagen). Most of the supersaturated specimens calcified the collagen, whereas none of the undersaturated ones did so. Among samples which calcified the collagen, the activity product of Ca"+ and HPO4 after incubation with collagen was essentially the same as that after incubation of the same specimen with brushite; it usually differed from that obtained after incubation with octacalcium phosphate or hydroxyapatite. The molar calcium-tophosphorus ratio of the solid phase in collagen was approximately 1. These results suggested that the solid phase formed in collagen is brushite. This conclusion was confirmed by the direct identification of brushite in collagen by X-ray diffraction.

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“…Besides these known substances, there are possibly other yet unidentified components present in urine which inhibit the formation of calcium phosphate (54,66,77,78). For a time, these inhibitors were thought to be of peptidic nature (58,(77)(78)(79), a theory which has recently been abandoned, the compounds studied being probably contaminants (66). Recently, phosphocitrate has been implicated in inhibition of calcium posphate formation.…”

Section: Inhibitors Of the Formation Of Calcium Phosphatementioning

confidence: 98%

Inhibitors and Promoters of Stone Formation

Fleisch

1981

Advances in Nephrourology

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Peptide inhibitors of calcium phosphate precipitation in the urine of normal and stone-forming men

Cited by 21 publications

References 7 publications

Spontaneous Precipitation of Brushite in Urine: Evidence that Brushite Is the Nidus of Renal Stones Originating as Calcium Phosphate

Spontaneous Precipitation of Brushite in Urine: Evidence that Brushite Is the Nidus of Renal Stones Originating as Calcium Phosphate

Calcification of collagen by urine in vitro: dependence on the degree of saturation of urine with respect to brushite

Inhibitors and Promoters of Stone Formation

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