Dietary Oxalate and Kidney Stone Formation

描述（由申请人提供）：肾结石疾病是一个严重的健康问题，每年消耗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，尿中的钙和草酸盐的量是该疾病的重要危险因素。直到最近，膳食中的草酸盐被认为对尿中草酸盐的量只有很小的贡献。然而，通过仔细控制饮食中草酸盐和其他营养物质的含量，我们能够证明它平均贡献了尿液中排泄的草酸盐的一半。本研究项目的目标是确定饮食中草酸盐如何最大程度地增加结石风险，并设计治疗策略，以抵消这种结石风险并防止结石复发。迄今为止，我们的研究表明，肾脏处理草酸盐的差异不会导致肾损伤或氧化应激，因为口服草酸盐负荷产生的草酸盐过滤负荷短暂增加。我们确实观察到饮食中草酸盐的吸收确实因人而异，特别是在大肠中的吸收。该项目的第一个目的是确定正常人和结石形成者中吸收过度的患病率，并确定与这种吸收过度相关的特征。第二个目的是阐明草酸盐降解微生物--产草酸盐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治疗。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并降低结石风险。这种基于实验室的结果翻译到临床应该是adatable减少一些饮食相关的风险因素，并在个人与结石草酸钙以外。

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.