Circadian Rhythm Disruption and Bisphosphonates as risk factors for Kidney Stones

项目摘要 肾结石很常见，也很昂贵。它们与剧烈的疼痛有关，并增加了 慢性肾脏疾病、高血压和冠心病。尽管这很重要，但还有 许多人不知道结石的风险因素，预防措施也是有限的。我们建议 研究两个新因素，昼夜节律紊乱和双磷酸盐药物，以及 护士健康研究II队列中肾结石形成的相关性。中途中断 昼夜节律，就像上夜班一样，可能是肾结石的一个可改变的危险因素，因为 已知的肾功能昼夜变化和肾结石风险，褪黑素之间的关联 受体和复发性肾结石，以及褪黑素对尿钙的可能降低作用。 尿钙水平越高，患肾结石的风险越高。双膦酸根 药物还可以降低尿钙；如果它们还能降低肾结石的风险，这可能是一种新的 含钙肾结石患者的预防选择。在目标1中，我们将研究 轮班工作与肾结石形成的关系。我们假设上夜班的工作将是 与肾结石形成的风险较高有关。在目标2中，我们将研究双膦酸盐的用途和 患肾结石的风险。我们还将使用尿样进行横断面分析，以比较平均 使用和不使用双膦酸类药物的受试者之间的尿钙水平。我们假设 使用双膦酸盐将与较低的肾结石形成风险和较低的平均尿量相关 钙的排泄。确定其他风险因素并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 和提供者。

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.