Dietary Oxalate and Kidney Stone Formation

描述(由申请人提供)：草酸钙肾结石的形成在美国影响着相当数量的个人，并为医疗保健费用贡献了数十亿美元。尿草酸排泄在这些结石的形成中起主要作用，因为它影响到尿液中草酸钙的过饱和，而草酸钙是形成草酸钙结石的先决条件。最近的研究表明，相当数量的尿草酸来自饮食来源。因此，减少草酸盐的摄入或从肠道吸收草酸盐可能被证明是限制个人形成结石风险的有用方法。用培养的细胞和动物模型进行的实验表明，草酸盐有可能通过产生被称为氧化自由基的化学物质来损害肾组织。这一过程可能在草酸钙结石的形成中起到致病作用。因此，减弱这种反应也可能限制结石的产生。这项研究提案有三个具体目标。第一个是比较形成结石和非形成结石的成年人对饮食草酸盐的反应。第二个目的是比较上述两组患者的肾草酸清除量。这些研究将确定这两组人在肾脏对草酸的处理上是否有任何差异。第三个目标是确定钙补充剂、维生素E补充剂、草酸降解菌的使用或所有这三种方法的组合是否可以减少尿草酸排泄和肾近端小管细胞损伤。所有这些研究都将在我们的综合临床研究中心进行，在那里可以进行严格控制的饮食。将评估各种反应，包括胃肠道草酸吸收、尿液过饱和、草酸排泄、氧化应激和肾近端小管细胞损伤的标志物。这些研究将有助于制定预防肾结石形成的策略。

DESCRIPTION (provided by applicant): Calcium oxalate kidney stone formation affects a significant number of individuals in the United States and contributes billions of dollars to health care costs. Urinary oxalate excretion plays a major role in the formation of these calculi as it influences the supersaturation of urine with calcium oxalate, a prerequisite for calcium oxalate stone formation. Recent investigations have shown that a significant amount of urinary oxalate is derived from dietary sources. Therefore, reducing oxalate consumption or its absorption from the intestinal tract may prove to be useful methods for limiting an individual's risk of forming stones. Experiments with cultured cells and animal models have demonstrated that oxalate has the potential to damage renal tissue through the generation of chemicals called oxygenated free radicals. This process may play a causative role in calcium oxalate stone formation. Therefore, attenuating this response may also limit stone generation.There are three specific aims in this research proposal. The first is to compare the response of stone forming and non-stone forming adults to dietary oxalate. The second aim is to compare renal oxalate clearance in both of the aforementioned groups. These studies will determine whether there are any differences in the renal handling of oxalate between these two groups. The third aim is to determine whether urinary oxalate excretion and renal proximal tubular cell injury can be reduced with calcium supplements, vitamin E supplements, administration of oxalate degrading bacteria, or a combination of all three of these regimens. All of these studies will be conducted in our General Clinical Research Center where carefully controlled diets can be administered. Various responses will be assessed including gastrointestinal oxalate absorption, urinary supersaturation, oxalate excretion, oxidative stress and markers of renal proximal tubular cell injury. These studies will aid in the development of strategies to prevent kidney stone formation.