Dietary Oxalate and Kidney Stone Formation

描述（由申请人提供）：草酸钙肾结石的形成影响了美国相当多的人，并为医疗保健成本贡献了数十亿美元。尿草酸盐排泄在这些结石的形成中起主要作用，因为它影响尿中草酸钙的过饱和，这是草酸钙结石形成的先决条件。最近的研究表明，大量的尿草酸盐来自饮食来源。因此，减少草酸盐的消耗或其从肠道的吸收可能被证明是限制个体形成结石的风险的有用方法。用培养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着重要作用。因此，减弱这种反应也可能限制结石的产生。第一个是比较结石形成和非结石形成成人对饮食草酸盐的反应。第二个目的是比较上述两组的肾草酸清除率。这些研究将确定这两组之间肾脏对草酸盐的处理是否存在任何差异。第三个目的是确定是否可以减少尿草酸排泄和肾近端肾小管细胞损伤与钙补充剂，维生素E补充剂，草酸降解细菌的管理，或所有这三种方案的组合。所有这些研究都将在我们的综合临床研究中心进行，在那里可以仔细控制饮食。将评估各种反应，包括胃肠道草酸盐吸收、尿过饱和、草酸盐排泄、氧化应激和肾近端肾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.