Circadian Rhythm Disruption and Bisphosphonates as risk factors for Kidney Stones

昼夜节律紊乱和双磷酸盐是肾结石的危险因素

• 批准号: 9357374
• 负责人: Megan L Prochaska
• 金额: $ 8.13万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357374
• 关键词: Address; Affect; Alleles; Animal Model; Bone Density; Calcium; Chronic Kidney Failure; Circadian Rhythms; Collection; Coronary heart disease; Cross-Sectional Studies; Crystallization; Disease; Environmental Risk Factor; Female; Frequencies; Genetic; Hormones; Hour; Human; Hypertension; Kidney Calculi; Knowledge; Melatonin; Melatonin Receptors; Metabolism; Minerals; Nurses' Health Study; Pain; Participant; Patients; Pharmaceutical Preparations; Prevention; Prevention strategy; Provider; Recurrence; Renal function; Risk; Risk Factors; Sampling; System; Urine; Variant; Work; bisphosphonate; bone; calcium excretion; calcium metabolism; cohort; cost; follow-up; high risk; innovation; lifetime risk; modifiable risk; novel; shift work; urinary

Project Summary Kidney stones are common and costly. They are associated with severe pain, and increased rates of chronic kidney disease, hypertension, and coronary heart disease. Despite this importance, there is much that is not known about stone risk factors and preventative options are limited. We propose to study two novel factors, circadian rhythm disruption and bisphosphonate medications, and the association with kidney stone formation within the Nurses’ Health Study II cohort. Disruptions in circadian rhythm, as in night shift work, may be a modifiable risk factor for kidney stones because of the known diurnal variation in kidney function and kidney stone risk, association between a melatonin receptor and recurrent kidney stones, and the possible lowering effect of melatonin on urinary calcium. Higher urinary calcium levels are associated with increased risk of kidney stones. Bisphosphonate medications may also reduce urinary calcium; if they also reduce kidney stone risk, this could be a new preventative option for patients with calcium-containing kidney stones. In Aim 1, we will examine the association between shift work and kidney stone formation. We hypothesize that night shift work will be associated with higher risk of kidney stone formation. In Aim 2, we will study bisphosphonate use and risk of kidney stones. We will also do a cross-sectional analysis using urine samples to compare mean urinary calcium levels between participants using and not using bisphosphonates. We hypothesize that bisphosphonate use will be associated with lower risk of kidney stone formation and lower mean urinary calcium excretion. Characterizing additional risk factors and identifying novel treatments will contribute to understanding of kidney stone formation and provide additional preventative strategies for patients and providers.

项目概要 肾结石很常见，而且费用高昂。它们会引起剧烈疼痛，并导致肾结石发病率增加。 慢性肾病、高血压和冠心病尽管如此重要，但仍然存在。 关于结石风险因素还有很多未知之处，我们建议的预防措施也很有限。 研究两个新因素，昼夜节律破坏和双磷酸盐药物，以及 护士健康研究 II 队列中与肾结石形成的关联。 昼夜节律，如夜班工作，可能是肾结石的一个可改变的危险因素，因为 已知肾功能的昼夜变化和肾结石风险，褪黑激素之间的关联 受体和复发性肾结石，以及褪黑激素对尿钙的可能降低作用。 较高的尿钙水平与双磷酸盐的风险增加有关。 药物也可能会降低尿钙；如果它们也能降低肾结石的风险，那么这可能是一种新的治疗方法。 含钙肾结石患者的预防选择 在目标 1 中，我们将检查 我们冒着夜班工作与肾结石形成之间的关联。 与较高的肾结石形成风险相关。在目标 2 中，我们将研究双磷酸盐的使用和 我们还将使用尿液样本进行横断面分析来比较平均值。 使用和不使用双磷酸盐的参与者之间的尿钙水平。 使用双膦酸盐可降低肾结石形成的风险并降低平均尿量 钙排泄的特征和确定新的治疗方法将有助于 了解肾结石的形成并为患者提供额外的预防策略 和提供商。