Enlargement of a lower pole calcium oxalate stone: a theoretical examination of the role of crystal nucleation, growth, and aggregation.

BACKGROUND AND PURPOSE

Nucleation, growth, and aggregation are considered to be the principal crystallization mechanisms in stone development. It is important to understand their relative significance so that appropriate experimental models can be used, and to identify the best therapeutic targets. The aim of this study was to explore a simplistic model of precipitation and aggregation and to determine the impact of these processes on crystal size density (CSD) and stone growth.

METHODS

The computer model represents a lower pole calcium oxalate stone and takes into account the limitations imposed by the amount of available oxalate.

RESULTS

Stone enlargement is a result of direct precipitation onto the stone or aggregation of suspended crystals. About one third of the available oxalate needs to be precipitated to form a clinically significant stone within a realistic time frame. If all crystallization is directly at the stone surface, then crystal growth rates are limiting for stones less than about 1 mm, and aggregation of suspended particles would be required for significant enlargement. For crystals in suspension, the CSD is taken to result from two mixed-suspension, mixed-product removal crystallizers operating in series. Using realistic values for nucleation and growth rate, the CSD can be consistent with precipitation of a significant proportion of the available oxalate. This CSD is modified by aggregation, which is assumed to be proportional to the number and volume of crystals in each size range, and further modified by considering the aggregation to be shared by stone enlargement and polymerization in suspension.

CONCLUSION

The variables in the model are the probability of aggregation, its rate, and the distribution between aggregation in suspension and onto the stone. Under some circumstances, the bimodal CSD of crystalluria seen in stone forming patients can be reproduced.