Mechanisms of disordered citrate and oxalate excretion in nephrolithiasis

肾结石柠檬酸盐和草酸盐排泄紊乱的机制

• 批准号: 10602545
• 负责人: Megan L Prochaska
• 金额: $ 18.6万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602545
• 关键词: Acids; Advisory Committees; Affect; Agreement; Alkalies; Alkalosis; Award; Basic Science; Biological Models; Calcium Oxalate; Chicago; Chronic; Citrates; Clinical Management; Clinical Research; Colon; Creatinine; Crystal Formation; Data; Development; Diet; Disease; Environment; Epidemiologic Methods; Epidemiology; Equilibrium; Excretory function; Fatty acid glycerol esters; Funding; Future; Gastric Bypass; Goals; Healthcare; Hour; Human; Hyperoxaluria; Impairment; Inflammation; Intervention Studies; Intestinal Absorption; Kidney; Kidney Calculi; Knowledge; Label; Lead; Learning; Link; Malabsorption Syndromes; Measures; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic acidosis; Morbidity - disease rate; Nephrolithiasis; Obesity; Oral; Oxalates; Patient Care; Patient risk; Patients; Permeability; Physicians; Physiology; Plants; Positioning Attribute; Prevention; Prevention strategy; Preventive care; Protocols documentation; Provider; Research; Research Design; Research Personnel; Risk; Risk Factors; Scientific Advances and Accomplishments; Serum; Sodium; Source; Testing; Training; Treatment Protocols; United States National Institutes of Health; Universities; Urine; absorption; bariatric surgery; base; career development; citrate carrier; clinical care; clinical practice; cost; design; dietary; epidemiologic data; experience; follow-up; gastrointestinal; high risk; improved; patient oriented; patient oriented research; patient retention; potassium citrate; prevent; primary endpoint; recruit; secondary endpoint; skills; translational study; urinary

Project Abstract Kidney stones are a major cause of morbidity and account for $11 billion in health care spending in the U.S. Low urine citrate and high urine oxalate both increase risk of stone formation. Mechanisms that regulate renal citrate and oxalate excretion affect kidney stone risk. Physicians use knowledge of mechanisms for stone prevention (e.g. potassium citrate to raise urine citrate, low oxalate diet to lower urine oxalate). The overall objective of this proposal is to expand our knowledge of mechanisms contributing to low urine citrate and high urine oxalate. This will advance scientific knowledge and improve kidney stone prevention strategies. The proposal will include study of mechanisms in two patient groups that are at high risk for kidney stones: obesity and Roux-en-Y gastric bypass (RYGB). Studying risk in these patient groups is important as obesity and bariatric surgery rates are on the rise in the U.S. This study will test the effect of diet on the association between higher urine oxalate and higher urine citrate in non-kidney stone patients that is disrupted in kidney stone patients. This will lead to future studies including testing the oxalate and citrate association under conditions of alkalosis. This may change clinical practice with new strategies such as providing alkali simultaneously with dietary oxalate to improve oxalate-citrate balance. It will also test the contribution of diet and paracellular gastrointestinal oxalate absorption to high urine oxalate in obese and RYGB kidney stone patients. This will lead to improved clinical care by focusing providers on higher yield strategies. Future studies will test these strategies. Furthermore, this study and support from the K23, will be vital to my career development. I will learn how to apply epidemiologic data to clinical research center (CRC) based human studies to investigate mechanisms responsible for the epidemiologic findings. I will learn how to design, implement, and conduct such studies, how to recruit and retain patients, and how to analyze repeated measures data. I will learn about management of kidney stone patients and high risk obese and bariatric surgery patients from a patient-centered perspective. I am in a rich research environment at the University of Chicago. I have developed a strong mentorship team with world experts in human based studies of kidney stone physiology and CRC study design and implementation. My advisory team includes world leaders in basic science, translational, and human studies related to citrate and oxalate and an expert in bariatric surgery. This team will support my scientific and professional development. At the end of the K23 award, I will be prepared to use the data collected to apply for an R01 in a follow up intervention study that I will lead as an independent investigator. My future studies will build on the data and skills I learned from this study. Therefore, through the research experience, training, and mentorship from this award, I will become a leader in kidney stones research and clinical management, including obese and bariatric surgery patients, with the ultimate goal to improve patient care.

项目摘要 肾结石是发病的主要原因，在美国占110亿美元的医疗保健支出。 低尿柠檬酸盐和高尿草酸盐都会增加结石形成的风险。调节肾脏的机制 柠檬酸盐和草酸盐排泄影响肾结石风险。医生利用对结石形成机制的了解 预防（例如，柠檬酸钾以提高尿柠檬酸盐，低草酸饮食以降低尿草酸盐）。整体 这项提案的目的是扩大我们对导致低尿柠檬酸盐和高尿柠檬酸盐的机制的了解。 尿草酸盐这将促进科学知识和改善肾结石预防策略。的 该提案将包括研究两个肾结石高危患者群体的机制：肥胖 和Roux-en-Y胃旁路术（RYGB）。研究这些患者群体的风险是重要的， 在美国，减肥手术率正在上升。这项研究将测试饮食对减肥手术的影响。 非肾结石患者的高尿草酸盐和高尿柠檬酸盐之间的关系， 结石患者这将导致未来的研究，包括测试草酸盐和柠檬酸盐协会下， 的条件。这可能会改变临床实践的新策略，如提供碱 同时与膳食草酸盐一起改善草酸盐-柠檬酸盐平衡。它还将测试饮食的贡献 肥胖和RYGB肾结石患者的高尿草酸与细胞旁胃肠道草酸吸收有关 患者这将通过将提供者集中在更高的收益策略上来改善临床护理。未来的研究 将测试这些策略。此外，K23的学习和支持对我的职业生涯至关重要。 发展我将学习如何将流行病学数据应用于临床研究中心（CRC）的人类 研究调查流行病学调查结果的机制。我将学习如何设计， 实施和进行此类研究，如何招募和留住患者，以及如何分析重复的 测量数据。我将学习如何处理肾结石患者和高风险肥胖和减肥 以病人为中心的外科手术。我是在一个丰富的研究环境中的大学， 芝加哥。我已经建立了一个强大的导师团队，与世界各地的专家在人体肾脏研究 结石生理学和CRC研究设计和实施。我的顾问团队包括世界各国的领导人， 柠檬酸盐和草酸盐相关的科学、转化和人体研究以及减肥手术专家。这 团队将支持我的科学和专业发展。在K23颁奖结束时，我将准备 我将使用收集的数据申请R 01进行一项随访干预研究，我将作为一名独立研究员领导该研究。 调查员我未来的研究将建立在我从这项研究中学到的数据和技能的基础上。因此通过 研究经验，培训和指导，从这个奖项，我将成为一个领导者在肾结石 研究和临床管理，包括肥胖和减肥手术患者，最终目标是 改善病人护理。