Crystallisation of calcium phosphate and calcium oxalate in solutions simulating the composition at different levels of the nephron
Abstract: Calcium oxalate (CaOx) is the most common constituent of urinary calcium stones, but in many such stones calcium phosphate (CaP) is also present and often located in the centre. From these observations it has been assumed that CaP is important in the process that leads to the development of a calcium stone and furthermore that the initial steps in this crystallisation take place in the nephron. The present investigation was undertaken to assess the risk of crystallisation of calcium salts at different nephron levels.Calculation of the ion-activity products of CaOx and different CaP salts Wlder solution conditions corresponding to those at various nephron levels, disclosed that the saturation with CaP was relatively higher than that of CaOx in the proximal tubule (PT), as well as in the proximal (DTp) and distal parts (DTd) of the distal tubule. Supersaturation concentrations necessary for the formation of CaOx crystals were recorded only in solutions with a composition corresponding to that in the collecting duct (CD).With an increased calcium concentration CaP was the crystal phase that most easily formed under solution conditions that corresponded to those at nephron levels above the CD. The relative risk of crystallisation of CaP was greatest in DTd~Urine. In CD-solutions CaOx was the preferred crystal type. Precipitation of CaOx in the lower part of CD and in final urine might be the result either of a primary nucleation of CaOx in the presence of a sufficiently high CaOx supersaturation or of a heterogeneous nucleation induced by CaP crystals formed at higher nephron levels.The nucleation of CaP and CaOx accomplished by reduction of volume of DTd- and CD- urine was apparently promoted by the urinary macromolecules in dialysed urine (dU). These macromolecules also inhibited the aggregation of CaP in solutions with a composition similar to that of urine in the distal tubule (DTd) and might counteract stone formation by inhibiting the growth and aggregation of both CaOx and CaP crystals during their passage through the CD. Furthermore, citrate had a direct inhibitory effect on the aggregation of CaP in DTd-solutions, an inhibitory effect that was additive to that of dU at concentrations of citrate above 0.5 mmol/L.The result~ obtained in these experimental studies support the hypothesis that CaP is the primary nucleus in mixed calcium stones. The process starts with the formation of CaP at a nephron level above the CD, possibly in DTd. A heterogeneous nucleation of CaOx is subsequently induced by dissolution of retained CaP crystals in the acid urine in the CD. The heterogeneous nucleation is probably accomplished by an increased local CaOx supersaturation that occurs at the CaP crystal surface as a result of this dissolution.
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