Effect of weight loss on urinary oxalate excretion in obese calcium oxalate kidney stone formers

总结 在过去的4年中，美国肾结石的患病率急剧增加。 几十年来，现在困扰着8.8%的人口。肥胖现在影响着超过40%的美国人口， 肾结石的治疗方法有哪些？草酸钙是最常见的结石 肥胖组群的组成。尿草酸盐排泄显著影响此类结石的发展 我们和其他人已经证明，肥胖的肾结石患者的胆固醇水平更高。各种因素可以 影响尿液中排泄的草酸盐量，包括消耗的草酸盐量，其生物利用度， 膳食钙量、胃肠道和肾脏草酸盐处理以及内源性草酸盐合成。我们 发现肥胖似乎增加了内源性草酸盐的合成。其他人则报告说， 肠道屏障，这可能导致增强的细胞旁肠道摄取。肥胖似乎也会改变肾脏 近端肾小管功能因此，这些因素中的任何一个单独或与其他因素相结合， 尿草酸排泄增加。这项资助的中心假设是，减肥可以减少尿 草酸排泄虽然以前预防肾结石的饮食方法主要集中在 大量营养素和微量营养素，热量限制尚未采用。我们建议使用现有的 和有效的饮食减肥计划，Optifast VLCD®，在肥胖，成人草酸钙结石形成者 并制定了具体的目标，重点是这是否会促进减少 内源性草酸盐合成到尿草酸盐池，胃肠道草酸盐吸收减少， 肠通透性和/或肾草酸盐处理的改变。拟议的研究将在 与2个大州的结石病、代谢、营养、内分泌学和减肥专家合作 为这群受折磨的人提供照顾的机构。如果可行性研究的预期结果得以实现， 这将作为一个强大的平台，进行一项大型临床试验，最终可能会减少 结石病以及改善或逆转与肥胖相关的许多其他共病。

SUMMARY The prevalence of kidney stone disease has dramatically increased in the United States (US) over the last 4 decades, now afflicting 8.8% of the population. Obesity which now affects over 40% of the US population is a recognized risk factor for the development of kidney stones. Calcium oxalate is the most common stone composition in the obese cohort. Urinary oxalate excretion significantly impacts the development of such stones and we and others have demonstrated that it is higher in obese kidney stone formers. Various factors can influence the amount of oxalate excreted in urine including the amount of oxalate consumed, its bio-availability, amount of dietary calcium, gastrointestinal and renal oxalate handling, and endogenous oxalate synthesis. We have found that obesity appears to increase endogenous oxalate synthesis. Others have reported that it disrupts the intestinal barrier which could result in augmented paracellular gut uptake. Obesity also appears to alter renal proximal tubular function. Thus, any one of these factors alone or in combination with the others could drive increased urinary oxalate excretion. The central hypothesis of this grant is that weight loss can reduce urinary oxalate excretion. While previous dietary approaches for kidney stone prevention have focused on macronutrients and micronutrients, caloric restriction has not been employed. We propose using an established and effective dietary weight reduction program, Optifast VLCD®, in obese, adult calcium oxalate stone formers and have crafted specific aims that focus on whether this will promote a reduction of the contribution of endogenous oxalate synthesis to the urinary oxalate pool, a decrease in gastrointestinal oxalate absorption and gut permeability, and/or alterations in renal oxalate handling. The proposed studies will be conducted in collaboration with experts in stone disease, metabolism, nutrition, endocrinology and weight loss at 2 large state institutions who provide care for this afflicted cohort. If the anticipated results of this feasibility study are achieved, this will serve as a strong platform to undertake a large clinical trial which could eventuate in an attenuation of stone disease as well as improvement or reversal of the many other co-morbidities associated with obesity.