Adhesion Properties and Phase Transformations of Uric Acid Crystals

Abstract

Uric acid, a product of protein metabolism, is the most abundant organic component in human kidney stones. At least six different crystalline phases of uric acid have been identified in kidney stones. Anhydrous uric acid (UA) and uric acid dihydrate (UAD) are the most common. We characterize these crystals to understand crystal nucleation, growth, aggregation and adhesion phenomena related to stone formation.

Chemical force microscopy was used to investigate the adhesion on the largest plate face of UA single crystals. The adhesion forces between UA (100) and atomic force microscopy tips modified with hydrophobic, hydrophilic, and charged groups were quantified in model aqueous solutions and model urine solutions. The highest adhesion was found between UA (100) and cationic tips in both solutions. This highlights a major difference between molecular crystal surfaces (in this case a weak acid) and most other inorganic biominerals. Solution parameters such as ionic strength and pH were influential in the magnitude of adhesion force obtained.

Solution-mediated phase transformation of UAD to UA may be important in the physiologic deposition of kidney stones, since compositional analysis of numerous kidney stones reveals that UAD is rarely found in the absence of UA. Using a combination of X-ray, thermal and optical techniques, the kinetics of the transformation of pure UAD and doped UAD crystals were studied in model aqueous solutions and model urine solutions. UAD transformed to UA via a 2-step process; metastable UAD undergoes dissolution followed by nucleation and growth of the stable UA. Pure UAD transformed to UA within 48 hours at 37oC, but UAD doped with molecular dyes and physiologically relevant ions transformed more slowly. The presence of trace amounts of impurities appear to stabilize the UAD more than it affects the growth of UA. This in vitro study provides insight into how UAD may be stablilized in physiologic solution and demonstrates that the UAD to UA transformation kinetics occur on a time scale that may be relevant to kidney stone formation.