Assessment of Endogenous Oxalate Synthesis in Calcium Oxalate Kidney Stone Formers and Healthy Individuals

草酸钙肾结石形成者和健康个体内源性草酸盐合成的评估

基本信息

批准号：
10285848
负责人：
Sonia Fargue
金额：
$ 9.97万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-19 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10285848
关键词：
Address Adult Affect Ascorbic Acid Body mass index Calcium Oxalate Chromatography Chronic Kidney Failure Collection Consumption Continuous Intravenous Infusion Coupled Data Development Diet Disease Endogenous Factors Environmental Risk Factor Excretory function Female Frequencies Future Glycine Glycolates Goals Hour Human Hydroxyproline Individual Intake Intravenous infusion procedures Investigation Ions Kidney Kidney Calculi Lead Light Link Mass Spectrum Analysis Measurement Measures Metabolic Metabolic Pathway Methods Non obese Obesity Oxalates Patients Pilot Projects Play Population Prevalence Prevention Recurrence Research Risk Risk Factors Role Source Testing Therapeutic United States Urine absorption dietary dietary control glyoxylate healthy volunteer high body mass index lifestyle factors male novel therapeutic intervention obese person recruit secondary outcome stable isotope stem treatment strategy urinary

项目摘要

SUMMARY The frequency of kidney stones, of which idiopathic calcium oxalate (CaOx) kidney stones are the most common, is increasing in the United States, affecting 9% of the population. Environmental factors, lifestyle factors, diet and metabolic or endogenous factors are known to play a role in the risk of kidney stone disease. Urinary oxalate excretion influences risk of CaOx kidney stone formation and is derived from both dietary oxalate intake and endogenous oxalate synthesis. Studies have addressed the contribution of dietary oxalate to urinary oxalate excretion in healthy subjects, and demonstrated that dietary contribution can vary between 20 to 50%. However, studies examining the importance of endogenous oxalate synthesis are lacking for patients with CaOx stone disease. Obesity is linked to CaOx kidney stone risk and may influence urinary oxalate excretion, although the underlying mechanisms are unknown. Strategies for treatment and prevention of CaOx kidney stones and research into new treatments would benefit from a better understanding of the sources of endogenous oxalate synthesis. The current proposal aims to determine if calcium oxalate kidney stone formers and subjects with obesity have increased rates of endogenous oxalate synthesis compared with healthy volunteers with normal BMI. An accurate measurement of endogenous oxalate synthesis will be performed using primed, steady-state, continuous intravenous infusion of the stable isotope of oxalate, 13C2-oxalate, and analysis by ion chromatography coupled with mass spectrometry, in subjects on a controlled low oxalate diet. 24-hr urinary oxalate excretions collected on a low oxalate, controlled diet will be compared with the measurement of the endogenous oxalate synthesis rate calculated by the continuous 13C2-oxalate intravenous infusion method. This comparison will determine if the utilization of a low oxalate diet and collection of 24 hour urine is an appropriate and easier approach to assess endogenous oxalate synthesis. The results of this pilot study will form the basis for a future R01 application to, 1), test the hypothesis that CaOx kidney stone formers have increased endogenous oxalate synthesis, 2), test the hypothesis that obesity enhances endogenous oxalate synthesis, and, 3), identify sources of endogenous oxalate synthesis that are altered in obese individuals and those with CaOx kidney stone disease, which in turn may lead to the development of novel therapeutic approaches to decrease urinary oxalate excretion.

概括肾结石的频率，其中特发性草酸钙（CAOX）肾结石是最常见的美国正在增加，占9％的人口。众所周知，代谢或内源性因素在肾脏疾病的风险中起作用排除会影响Caox肾结石形成的风险，并源自饮食中草酸盐的摄入量和内源性草酸盐合成。然而，健康受试者的排名和饮食贡献可能在20％到50％之间。缺乏研究内源性草酸盐合成重要性的研究对Caox石头患者缺乏疾病。潜在的机制是未知的。对新疗法的研究将受益于对内源性草酸盐来源的更好理解合成。与正常的健康志愿者相比 BMI。连续静脉注射草酸盐，13c2-Oxalate的稳定同位素和离子分析在控制低氧饮食的受试者中，色谱与质谱相结合将在低氧酸盐，控制饮食中收集的草酸盐排泄与其测量的测量。通过连续13c2-氧化静脉输注法计算的血氧酸盐合成速率比较将确定低氧饮食的利用和24小时尿液的收集是否合适更容易评估香水合成的方法。对于未来的R01应用程序，1）检验了Caox肾结石增加的假设内源性草酸盐合成，2），检验了增强内源草酸盐合成的假设， 3），确定肥胖个体和患有的那些人的内源性草酸盐合成来源 Caox肾脏石材疾病反过来可能导致新的治疗方法发展为减少草酸盐排泄。