Revisiting Uric Acid Stone Dissolution Kinetics: Insights for Optimizing Medical Therapy.

Background and objective: Urine alkalinization, the mainstay of uric acid (UA) stone dissolution medical therapy, relies on old in vitro studies and expert opinions. Moreover, the effects of lowering urine UA concentration in patients without hyperuricosuria have rarely been investigated. We revisited the UA dissolution kinetics to determine the optimal alkalinization target and evaluate the effect of reducing urine UA saturation below normal levels. Methods: Ultraviolet-visible spectrophotometry was employed to analyze the dissolution kinetics of intact and grounded stones in artificial urine solution at various pH levels and UA concentrations. Crystal structures of precipitates were examined by X-ray diffraction. Key findings and limitations: The average dissolution rate increased fourfold when the pH rose from 6-6.5 to 6.5-7 and ninefold when it reached 7-7.2, with the optimal level being at 7.2. At pH 7.4, the rate dropped significantly, and hydroxyapatite crystals precipitated. Grounded stones dissolved 10-fold faster than intact stones at each pH level. Lowering of the urine UA concentration enhanced the dissolution rate only at pH >6.5 and after reducing the concentrations by 55% of the normal level. The artificial urine, buffering solution, and model could only partially mimic the in vivo urine environment. Conclusions and clinical implications: The in vitro study of UA dissolution kinetics offers valuable insights for improving medical therapy in patients with UA nephrolithiasis. Our study confirms alkalinization as the key factor for dissolution and supports expert recommendations. Specifically, by maintaining urine pH >6.5, preferably 7-7.2, and increasing stone surface area, dissolution can be optimized. Reduction of UA concentrations in patients without hyperuricosuria enhances dissolution only after sufficient alkalinization. Patient summary: In this report, we used contemporary laboratory methods to refine the optimal pH target of urine alkalinization, the mainstay medical therapy for uric acid stone dissolution. We found the dissolution rate to increase mainly at pH levels above 6.5, with the optimal pH being 7.2. Additionally, increasing the stone surface area by fragmentation increased the dissolution further, implicating a potential second-line option when initial treatment is unsuccessful. Finally, we confirmed the expert-based recommendation on the lack of effectiveness of allopurinol treatment without adequate alkalinization in patients who have normal uric acid urinary excretion.