An understanding of renal stone development in a mixed oxalate-phosphate system

Abstract

The in vivo formation of calcium oxalate concretions having calcium phosphate nidi is simulated in an in vitro (37 degrees C, pH 6.0) dual constant composition (DCC) system undersaturated (sigma DCPD = -0.330) with respect to brushite (DCPD, CaHPO 4 . 2H 2O) and slightly supersaturated (sigma COM = 0.328) with respect to calcium oxalate monohydrate (COM, CaC2O4 . H2O). The brushite dissolution provides calcium ions that raise the COM supersaturation, which is heterogeneously nucleated either on or near the surface of the dissolving calcium phosphate crystals. The COM crystallites may then aggregate, simulating kidney stone formation. Interestingly, two intermediate phases, anhydrous dicalcium phosphate (monetite, CaHPO4) and calcium oxalate trihydrate (COT), are also detected by X-ray diffraction during this brushite-COM transformation. In support of clinical observations, the results of these studies demonstrate the participation of calcium phosphate phases in COM crystallization providing a possible physical chemical mechanism for kidney stone formation.

Figure 1

DCPD dissolution. (a) CC plot of titrant volume against time of DCPD dissolution in the absence of oxalate. X-ray diffraction patterns (inset) show that the undissolved phase is pure DCPD. (b) AFM image of DCPD dissolution in the absence of oxalate.

Figure 2

DCC crystallization plots in a mixed solution of calcium phosphate (σ_brushite = −0.330, red line) and oxalate (σ_COM = 0.326, green line). Stars mark the different stages at which the solid samples were taken. The black line shows a typical COM crystallization CC plot of titrant volume as a function of time in the absence of DCPD/phophate. XRD patterns (inset) indicate that the crystallites after nucleation and growth in the absence of phosphate are pure COM.

Figure 3

Comparison of the X-ray diffraction patterns for (a) DCPD seeds, a pure phase without other forms of calcium phosphate, (b) following DCPD dissolution in the presence of oxalate. The DCC experimental results showed the presence of an unexpected calcium phosphate phase, monetite (CaHPO₄). (c) Samples taken after 300 min of the DCC experiment showed calcium oxalate monohydrate with trace amounts of monetite and calcium oxalate trihydrate (COT).