Cannabis use and kidney health among veterans with coronary artery disease

项目总结 尽管广泛将用于医疗或娱乐用途的大麻合法化，并发展了一种 尽管大麻产业价值数十亿美元，但大麻对健康的影响还没有得到充分的表征。 实验证据支持大麻素系统在几种形式的慢性精神分裂症中的致病作用 肾脏疾病(CKD)和病例系列揭示了合成大麻素的使用与 急性肾损伤(AKI)。然而，目前尚缺乏关于甲型肝炎的流行病学证据。 大麻对肾脏健康的影响。以前的队列研究由于对大麻的评估不足而受到限制。 暴露、吸食大麻者暴露水平低或对肾脏健康结果的评估不完整。 向公众大规模销售大麻，扩大高效大麻产品的供应，以及 对于CKD患者来说，疼痛管理选择不足，评估其潜力至关重要 大麻的肾脏毒性或安全性。 这项建议将调查大麻的使用对心脏和大麻(THC)肾脏健康的影响 研究，当代和全国大麻使用者(N=1,132)和非使用者(N=2,863)队列， 冠状动脉疾病。作为出生队列的设计，THC研究确定了当前和终生 通过电话健康访谈了解所有参与者的大麻暴露情况，99%以上的参与者 同意后续联系以进行后续研究。以及这群人获得电子医疗服务的机会 对于临床结果的记录和住院诊断，THC研究提供了前所未有的 为我们拟议的肾脏健康调查提供了机会。第一个目标是评估 大麻暴露与慢性肾脏病的风险和肾功能在五年内的纵向变化。第二 AIM将在五年内研究大麻暴露与AKI风险的关系。最后，第三个目标将 在基线和一年后，使用一组尿液来探讨大麻的亚临床肾毒性 反映肾脏健康的五个不同组成部分的生物标志物：肾小球损伤；肾小管功能障碍；肾小管 损伤；肾小管炎症和纤维化；肾小管修复和储备。我们的调查小组有广泛的 这些生物标志物的经验及其在检测药物引起的肾毒性中的作用。这些 项目将：1)提供关于大麻的潜在肾毒性或安全性的重要数据；2)告知 传达大麻风险或益处的公共卫生信息；以及3)为 未来可能评估基于生物标记物的策略以监测人的大麻肾毒性的研究 有患慢性肾脏病的风险。

PROJECT SUMMARY Despite widespread legalization of cannabis for medicinal or recreational use and the development of a multibillion dollar cannabis industry, the health effects of cannabis are insufficiently characterized. Experimental evidence supports a pathogenic role of the cannabinoid system in several forms of chronic kidney disease (CKD) and case series have revealed a link between synthetic cannabinoid use and the risk of acute kidney injury (AKI). However, there is a dearth of epidemiologic evidence regarding the effects of cannabis on kidney health. Previous cohort studies have been limited by inadequate assessment of cannabis exposure, low exposure levels among cannabis users, or incomplete assessment of kidney health outcomes. With mass marketing of cannabis to the public, expanding availability of high potency cannabis products, and inadequate pain management options for persons with CKD, it is critically important to evaluate the potential kidney toxicity or safety of cannabis. This proposal will investigate the effects of cannabis use on kidney health in The Heart and Cannabis (THC) study, a contemporary and national cohort of cannabis users (N=1,132) and non-users (N=2,863) with coronary artery disease. Designed as a birth cohort, the THC study has ascertained current and lifetime cannabis exposure in all participants by telephone-based health interviews, and more than 99% of participants agreed to subsequent contact for study follow-up. Together with the cohort's access to electronic health records and hospitalization diagnoses for clinical outcomes, the THC study offers an unprecedented opportunity for our proposed investigations of kidney health. The first Aim will evaluate associations of cannabis exposure with risk of CKD and longitudinal changes in kidney function over five years. The second Aim will examine associations of cannabis exposure with risk of AKI over five years. Finally, the third Aim will explore subclinical nephrotoxicity of cannabis at baseline and after one year, using a panel of urinary biomarkers that capture five distinct components of kidney health: glomerular injury; tubular dysfunction; tubule injury; tubule inflammation and fibrosis; and, tubule repair and reserve. Our investigative team has extensive experience with these biomarkers and their utility for the detection of drug-induced nephrotoxicity. These projects will: 1) provide important data regarding the potential nephrotoxicity or safety of cannabis; 2) inform public health messages that communicate the risks or benefits of cannabis; and 3) lay the groundwork for future studies that could evaluate a biomarker-based strategy to monitor for cannabis nephrotoxicity in persons at risk for CKD.