Studies on the role of calcium phosphate in the process of calcium oxalate crystal formation

Abstract

Crystals of calcium phosphate (CaP) added to solutions with a composition corresponding to that at different levels of the collecting duct (CD) and with different pH were rapidly dissolved at pH 5.0, 5.25 and 5.5. Only minor or no dissolution was observed at higher pH levels. Despite this effect, CaP crystals induced nucleation or heterogeneous crystallization of CaOx up to a pH of 6.1, whereas CaP was the type of crystalline material that precipitated at higher pH. Accordingly, small crystal volumes were recorded at pH 5.5 and great volumes at pH 6.7 4 h after the addition of CaP crystals to the solutions. Dialyzed urine appeared to counteract the dissolution of CaP and to reduce the rate of secondary crystallization. The CaP induced crystallization of CaOx was confirmed by a reduction of (14)C-labeled oxalate in solution. The AP(CaOx) required for a nucleation or heterogeneous crystallization of CaOx in the presence of CaP was around 1.5 x 10(-8) (mol/l)(2). For CaP crystal formation on CaP, an AP(CaP) ((a)Ca(2+) x (a)PO(4)(3-)) of approximately 50 x 10(-14) (mol/l)(2) appeared to be necessary. The CaOx crystals formed were microscopically found in association with the CaP crystalline material and were most frequently of CaOx dihydrate type. Step-wise crystallization experiments comprising supersaturation with CaP (Step A), supersaturation with CaOx (Step B) and subsequently acidification (Step C) showed that CaOx crystal formation occurred when CaP crystals were dissolved and thereby served as a source of calcium. The ensuing formation of CaOx crystals is most likely the result from high local levels of supersaturation with CaOx caused by the increased concentration of calcium. These experimental studies give support to the hypothesis that crystallization of CaOx at lower nephron levels or in caliceal urine might be induced by dissolution of CaP formed at nephron levels above the CD, and that a low pH is prerequisite for the precipitation of CaOx. The observations accordingly provide additional evidence for the important role of calcium phosphate in the crystallization of calcium oxalate, that might occur both at the surface of Randall's plaques and intratubularly at the papillary tip.

Calcium Oxalate Stone Fragment and Crystal Phagocytosis by Human Macrophages

“…17 Interstitial CaOx depositions are typically seen in patients with primary or enteric hyperoxaluria. This type of CaOx is associated with extensive inflammation, 18 while interstitial aCaP deposition alone is not.…”

Biomimetic Randall’s plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation

“…In fact, RP as well as the stones themselves contain various amounts of proteins and polysaccharides, including albumin, globulin, Tamm-Horsfall glycoprotein (THP), prothrombin fragment 1, inter-a-trypsin inhibitor (bikunin), osteopontin (OPN), and calprotectin, all of which could conceivably contribute to forming an amorphous phase, or even a PILP-like phase, as demonstrated for various acidic polymers in our group [66–68]. These components are termed crystal matrix proteins, and constitute 1 5% of RP and urinary stones, implying that they may have some influence in the stone-formation process [10, 31, 34, 36, 38, 39, 41, 50, 51, 55, 69–71]. …”

“…These mineral plaques then spread into the interstitial tissue (Figure 2b), and as it grows it reaches and breaks through the papillary surface epithelium. It is then exposed to the urine, where the pH and ionic constituents differ, such that a new mineral phase of calcium oxalate is deposited on this plaque, resulting in stone formation [3, 4, 6–10, 12, 14, 18, 19, 24, 31–33]. …”

“…This group forms calcium oxalate renal stones without any systemic disorder and make up about 80% of all stone-formers [8, 16, 24, 31, 33, 39, 41, 42, 48–51]. The lack of a known cause (such as various urinary imbalances) for the majority of patients who develop stones also contributes to the difficulty of understanding and treating this painful and recurring disease.…”

“…A protein of great interest is osteopontin (OPN or uropontin, the urinary form of OPN), which has been shown to be important in the pathogenesis of renal stones and, as mentioned, has been identified as one of the proteins in the matrix layer [4, 7–9, 14, 27, 31, 36, 39, 41–43, 46]. It also has been shown to be present in the concentric laminations found in RP (where it was immunostained)[9].…”