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: 10449671
• 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/10449671
• 关键词: Acids; Advisory Committees; Affect; Alkalies; Alkalosis; Award; Basic Science; Biological Models; Calcium Oxalate; Chicago; Chronic; Citrates; Clinical Management; Clinical Research; Creatinine; Crystal Formation; Crystallization; 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; Non obese; 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; 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 肾结石是发病率的主要原因，占美国医疗保健支出的110亿美元。 低尿柠檬酸和高尿草酸都会增加结石形成的风险。调节肾脏的机制 柠檬酸盐和草酸盐的排泄会影响肾结石的风险。内科医生利用结石的机制知识 预防(例如，柠檬酸钾升高尿液柠檬酸，低草酸饮食降低尿草酸)。整体而言 这项建议的目的是扩大我们对导致低尿柠檬酸和高尿柠檬酸的机制的了解。 尿液草酸。这将提高科学知识，完善肾结石预防策略。这个 该提案将包括对两个肾结石高危患者组的机制进行研究：肥胖 Roux-en-Y胃转流术(RYGB)。研究这些患者群体的风险很重要，因为肥胖和 美国的减肥手术率正在上升。这项研究将测试饮食对这种联系的影响 非肾结石肾损害患者高尿草酸与高尿柠檬酸之间的关系 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在 碱中毒的情况。这可能会改变临床实践，采用新的策略，如提供碱 同时配合饲粮草酸，改善草酸-柠檬酸平衡。它还将测试饮食的贡献 肥胖和RYGB肾结石患者对高尿草酸的细胞旁胃肠草酸吸收 病人。这将通过将供应商的重点放在更高收益的策略上来改善临床护理。未来研究 将对这些策略进行测试。此外，K23的学习和支持对我的职业生涯也是至关重要的 发展。我将学习如何将流行病学数据应用于基于临床研究中心(CRC)的人类 调查流行病学发现的机制的研究。我会学习如何设计， 实施和实施此类研究，如何招募和留住患者，以及如何分析重复 测量数据。我将学习肾结石患者和高危肥胖及肥胖患者的管理。 手术患者以患者为中心的观点。我在密歇根大学有丰富的研究环境 芝加哥。我与世界各地的肾脏研究专家建立了一支强大的指导团队。 结石生理学和CRC研究的设计与实现。我的顾问团队包括Basic中的世界领导人 与柠檬酸盐和草酸盐相关的科学、翻译和人体研究以及减肥外科专家。这 团队将支持我的科学和专业发展。在K23奖项结束时，我将准备 使用收集的数据在后续干预研究中申请R01，我将作为独立研究人员领导该研究 调查员。我未来的研究将建立在我从这次研究中学到的数据和技能的基础上。因此，通过 通过这个奖项的研究经验、培训和指导，我将成为肾结石领域的领导者 研究和临床管理，包括肥胖和减肥手术患者，最终目标是 改善患者护理。