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

减肥对肥胖草酸钙肾结石形成者尿草酸排泄的影响

• 批准号: 10406340
• 负责人: DEAN GEORGE ASSIMOS
• 金额: $ 31.06万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406340
• 关键词: Acids; Adult; Affect; Attention; Biological Availability; Blood Pressure; Body Weight decreased; Body mass index; Calcium; Calcium Oxalate; Caloric Restriction; Caring; Chemicals; Clinical Research; Clinical Trials; Collaborations; Consumption; Data; Development; Diet; Dietary Calcium; Disease; Economics; Endocrinology; Energy Intake; Excretory function; Feasibility Studies; Grant; Hunger; Institution; Insulin Resistance; Intake; Intestinal permeability; Kidney; Kidney Calculi; Knowledge; Laboratory Research; Lipids; Liquid substance; Macronutrients Nutrition; Measurement; Medical; Metabolism; Methods; Micronutrients; Minerals; Nephrolithiasis; Obesity; Oral; Oxalates; Oxalobacter formigenes; Participant; Patient Recruitments; Permeability; Pilot Projects; Play; Population; Prevalence; Prevention; Quality of life; Recommendation; Reducing diet; Renal function; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Sodium; Texas; Tubular formation; United States; Universities; Urinary Calculi; Urine; Urology; Weight; absorption; adult obesity; attenuation; base; burden of illness; cohort; comorbidity; dietary; dietary approach; gastrointestinal; indexing; innovation; interdisciplinary approach; intestinal barrier; nephrogenesis; novel strategies; nutrition; programs; recruit; skills; time interval; uptake; urinary; weight loss program

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.

概括 过去 4 年，美国 (US) 的肾结石患病率急剧上升 几十年来，现在8.8%的人口受到影响。目前，肥胖已影响超过 40% 的美国人口 公认的肾结石形成的危险因素。草酸钙是最常见的结石 肥胖队列的组成。尿液中草酸盐的排泄显着影响此类结石的形成 我们和其他人已经证明，肥胖肾结石形成者的这一比例更高。各种因素都可以 影响尿液中草酸盐的排出量，包括草酸盐的消耗量、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 发现肥胖似乎会增加内源性草酸盐的合成。其他人报告说它扰乱了 肠道屏障可能导致细胞旁肠道吸收增加。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结合都可能驱动 尿草酸排泄增加。这项资助的中心假设是减肥可以减少尿 草酸盐排泄。虽然以前预防肾结石的饮食方法主要集中在 常量营养素和微量营养素，尚未采用热量限制。我们建议使用既定的 以及针对肥胖、成人草酸钙结石形成者的有效饮食减肥计划 Optifast VLCD® 并制定了具体目标，重点关注这是否会导致减少 内源性草酸盐合成到尿草酸盐库，胃肠道吸收草酸盐减少， 肠道通透性和/或肾脏草酸盐处理的改变。拟议的研究将在 与两个大州的结石病、代谢、营养、内分泌和减肥方面的专家合作 为这一受苦人群提供护理的机构。如果本次可行性研究达到预期结果， 这将成为进行大型临床试验的强大平台，最终可能会减弱 结石病以及与肥胖相关的许多其他并发症的改善或逆转。