Lotan Paz, Mastai Michael, Mastai Yitzhak, Aloni Sapir Shekef, Sagy Itay, Sivan Bezalel, Darawsha Abd E, Lifshitz David
Department of Urology, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.
Department of Urology, Rabin Medical Center, Petach Tikva, Israel.
Eur Urol Open Sci. 2025 Apr 28;76:38-44. doi: 10.1016/j.euros.2025.04.003. eCollection 2025 Jun.
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.
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.
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.
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.
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.
尿液碱化是尿酸（UA）结石溶解药物治疗的主要手段，其依据是以往的体外研究和专家意见。此外，很少有人研究在无高尿酸尿症患者中降低尿液UA浓度的效果。我们重新审视了UA溶解动力学，以确定最佳碱化目标，并评估将尿液UA饱和度降低至正常水平以下的效果。
采用紫外可见分光光度法分析完整结石和磨碎结石在不同pH值和UA浓度的人工尿液溶液中的溶解动力学。通过X射线衍射检查沉淀物的晶体结构。
当pH值从6 - 6.5升至6.5 - 7时，平均溶解速率增加了四倍，当达到7 - 7.2时增加了九倍，最佳水平为7.2。在pH值为7.4时，速率显著下降，并且有羟基磷灰石晶体沉淀。在每个pH水平下，磨碎的结石溶解速度比完整结石快10倍。仅在pH值>6.5且将浓度降低至正常水平的55%之后，降低尿液UA浓度才会提高溶解速率。人工尿液、缓冲溶液和模型只能部分模拟体内尿液环境。
UA溶解动力学的体外研究为改善UA肾结石患者的药物治疗提供了有价值的见解。我们的研究证实碱化是溶解的关键因素，并支持专家建议。具体而言，通过维持尿液pH值>6.5，最好是7 - 7.2，并增加结石表面积，可以优化溶解。在无高尿酸尿症患者中，仅在充分碱化后，降低UA浓度才会增强溶解。
在本报告中，我们使用当代实验室方法完善了尿液碱化的最佳pH目标，尿液碱化是尿酸结石溶解的主要药物治疗方法。我们发现溶解速率主要在pH值高于6.5时增加，最佳pH值为7.2。此外，通过破碎增加结石表面积可进一步提高溶解，这意味着在初始治疗失败时可能是一种二线选择。最后，我们证实了基于专家的建议，即在尿酸尿排泄正常的患者中，如果没有充分碱化，则别嘌醇治疗无效。
