Dietary Oxalate and Kidney Stone Formation

描述(申请人提供)：肾结石疾病是一个严重的健康问题，每年花费数十亿美元的医疗保健费用和生产力损失。这些结石的大部分主要由草酸钙组成。因此，尿中钙和草酸的含量是该病的重要风险因素。直到最近，人们还认为，饮食中的草酸对尿液中的草酸含量只有很小的贡献。然而，使用仔细控制草酸和其他营养物质含量的饮食，我们能够证明它平均贡献了尿液中草酸排泄的一半。这项研究项目的目标是确定饮食中草酸对结石风险的最大贡献，并设计能够抵消这种结石风险并防止Stobe复发的治疗策略。到目前为止，我们的研究表明，在口服草酸盐负荷产生的草酸盐过滤负荷短暂增加后，肾脏处理草酸盐的差异不会导致肾脏损伤或氧化应激。我们确实观察到，饮食中草酸的吸收在不同的人身上确实不同，特别是发生在大肠的吸收。该项目的第一个目标是确定正常人和结石形成者中高吸收的流行率，并确定哪些特征与这种高吸收有关。第二个目的是阐明草酸降解微生物--草酸杆菌在大肠吸收中的作用。第三个目标是将这些发现转化为预防结石复发的定向疗法。我们将测试一个基于互联网的互动程序，该程序将利用几种饮食调整来帮助患者调整饮食，降低结石风险。将基于实验室的研究结果转化为临床应该适用于减少一些饮食相关的危险因素，并适用于患有草酸钙以外的结石的个体。

DESCRIPTION (provided by applicant): Kidney stone disease is a significant health problem that consumes billions of dollars annually in health care costs and lost productivity. The bulk of these stones consist primarily of calcium oxalate. The amount of calcium and oxalate in urine are thus significant risk factors for the disease. Until recently, dietary oxalate was believed to make only a minor contribution to the amount of oxalate in urine. However, using diets carefully controlled in their content of oxalate and other nutrients, we were able to show that it contributed on average half of the oxalate excreted in urine. The goal of this research project is to determine how dietary oxalate most contributes to stone risk and to design therapeutic strategies that will offset this stone risk and prevent stobe recurrence. To date, our investigations have shown that differences in the renal handling of oxalate do not contribute to renal injury or oxidative stress following transient increases in the filtered load of oxalate produced by oral oxalate loads. We did observe that the absorption of dietary oxalate does differ in individuals, particularly that occurring in the large intestine. The first aim of this project is to identify the prevalence of hyperabsorption in normal individuals and stone formers and to determine what features are associated with this hyperabsorption. The second aim is to clarify the role of the oxalate-degrading organism, Oxalobacter formigenes in large intestinal absorption. The third aim seeks to translate these findings into directed therapies that prevent stone recurrence. We will test an interactive Internet-based program that will utilize several dietary modifications to help patients modify their diet and reduce stone risk. This translation of laboratory based findings to the clinic should be adatable to reducing a number of dietary associated risk factors and in individuals with stones other than calcium oxalate.