In vitro calcium oxalate crystallisation methods.

In vitro calcium oxalate crystallisation has been, and will continue to be, of fundamental importance to urolithiasis research. Many different methods have been employed which differ qualitatively and quantitatively in the extent that they reproduce aspects of the renal system or in their ability to distinguish different aspects of crystallisation activity. Whatever system is used there are three key aspects that are worth bearing in mind. Firstly, a major controlling factor will be the prevailing supersaturation and other physicochemical considerations, secondly, during the course of the reaction different processes may come into play and thirdly, the processes we are trying to model take place in a dynamic biological environment. Different approaches to the study of crystallisation can be classified in many ways, such as the process or analytical technique but at a more fundamental level it is helpful to focus on the changes in supersaturation during the course of the reaction. A steady state supersaturation is more likely to be representative of the intra-renal situation than a system which decays to the equilibrium position. The constant composition method and the mixed suspension mixed product removal method both achieve a steady supersaturation.

Why does the Bonn Risk Index discriminate between calcium oxalate stone formers and healthy controls?

PURPOSE: The BRI has been shown to discriminate between calcium oxalate stone formers and controls. BRI is the ratio of the concentration of ionized calcium and the amount of oxalate that must be added to 200 ml urine to initiate crystallization. Higher BRI values are predictive of being a stone former and a value of 1.0 has been found to be the cutoff value to distinguish stone formers and controls. It is not easy to present a consistent argument based on the thermodynamics of calcium oxalate crystallization to account for the success of this index. For instance, why should 2 samples sharing the same BRI but with different ionized calcium and oxalate values have the same likelihood of being obtained from a stone former? MATERIALS AND METHODS: Using data on 195 samples the distribution and interrelationships of measured variables were examined. They were used to calculate illustrative data with which it was possible to examine the effects of varying the parameters and their relationships. RESULTS: Data simulations identified 3 necessary and sufficient conditions that must be met for BRI to be an effective discriminator between stone former and nonstone former urine samples. CONCLUSIONS: The success of BRI can be explained as the natural outcome of there being significantly different distributions (stone formers vs nonstone formers) of the concentration of ionized calcium and the formation product minus activity product difference as well as the correlation between these 2 variables.

Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones.

BACKGROUND: Alkaline citrate is thought to be helpful in reducing recurrences of calcium oxalate stones. The evidence for this is incomplete, there have been few good trials, all with their own limitations, and not all reported any significant benefit. In vitro studies are usually cited to support the clinical studies but these too have their drawbacks, in particular they relate to crystals and microscopic aggregates and not to actual stone growth. Here we test citrate in vitro using a model of macroscopic calcium oxalate stone enlargement. METHODS: Twelve calcium oxalate stones were grown at a time in a stone farm. Six were grown with 2 mmol/L citrate and six with 6 mmol/L citrate. Three protocols were tested; artificial urine, artificial urine with urinary macromolecules (UMM) from male controls and artificial urine with UMM from male stone formers. The stones were grown continuously for at least 24 days. RESULTS: In all three experiments the higher citrate concentration significantly reduced the growth rate of stones by more than 50% (P < 0.001). There was a small decrease in ionised calcium in the stone growth media (P < 0.001) and significant (P < 0.001) but small increase in pH (about 0.07 pH units). The inclusion of UMM also brought about a decrease in stone growth, particularly at 2 mmol/L citrate. CONCLUSION: Citrate inhibited stone growth in this laboratory model. This was true both in defined media and with addition of UMM. This adds to evidence justifying the use of alkaline citrate in calcium oxalate nephrolithiasis.