Dietary Oxalate and Kidney Stone Formation

描述（由申请人提供）：肾结石疾病是一个重大的健康问题，每年消耗数十亿美元的医疗费用和生产力损失。这些结石的主要成分是草酸钙。因此，尿液中钙和草酸盐的含量是该疾病的重要危险因素。直到最近，人们还认为饮食中的草酸对尿液中草酸含量的影响很小。然而，通过仔细控制草酸盐和其他营养物质的含量，我们能够证明它贡献了尿液中平均一半的草酸盐。本研究项目的目标是确定饮食草酸盐如何最大程度地促进结石风险，并设计治疗策略，以抵消这种结石风险并防止复发。迄今为止，我们的研究表明，在口服草酸负荷产生的草酸过滤负荷短暂增加后，肾脏对草酸处理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盐的吸收因人而异，尤其是在大肠中。该项目的第一个目的是确定正常个体和结石形成者中过度吸收的患病率，并确定与这种过度吸收相关的特征。第二个目的是阐明草酸降解生物，formigenes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治疗。我们将测试一个基于互联网的互动项目，该项目将利用几种饮食调整来帮助患者调整饮食，降低结石风险。将实验室研究结果转化为临床研究结果，应适用于减少一些与饮食相关的危险因素，并适用于除草酸钙以外的结石患者。

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.