Cannabis use and kidney health among veterans with coronary artery disease

患有冠状动脉疾病的退伍军人的大麻使用和肾脏健康

• 批准号: 10261058
• 负责人: Vasantha Kolavennu Jotwani
• 金额: $ 9.96万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261058
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adverse effects; Age; Albuminuria; American; Animal Model; Benefits and Risks; Biological Markers; Biopsy; Birth; CNR1 gene; CNR2 gene; Cannabinoids; Cannabis; Case Series; Chronic Kidney Failure; Cisplatin; Clinical; Cohort Studies; Coronary Arteriosclerosis; Data; Development; Diabetic Nephropathy; Diagnosis; Electronic Health Record; Enrollment; Epidemiology; Epithelial; Epithelium; Fibrosis; Follow-Up Studies; Functional disorder; Future; Glomerular Filtration Rate; Goals; Health; Heart; Heart Diseases; Homeostasis; Hospitalization; Human; IGA Glomerulonephritis; Individual; Industry; Inflammation; Injury; Interstitial Nephritis; Interview; Investigation; K2/Spice; Kidney; Kidney Diseases; Knowledge; Laboratories; Lead; Legal; Link; Marketing; Measures; Medical Marijuana; Medicare claim; Modernization; Monitor; Non-Steroidal Anti-Inflammatory Agents; Opioid Analgesics; Outcome; Pain; Pain management; Participant; Pathogenicity; Patients; Persons; Pharmaceutical Preparations; Plants; Play; Population; Prevalence; Proteinuria; Protocols documentation; Public Health; Recording of previous events; Renal function; Reporting; Risk; Role; Safety; System; Telephone; Tubular formation; Urine; Veterans; base; biomarker panel; clinical Diagnosis; clinical decision-making; cohort; design; diabetic; disorder risk; drug testing; endogenous cannabinoid system; epidemiology study; experience; experimental study; follow-up; high risk; improved; mRNA Expression; marijuana legalization; marijuana use; marijuana user; nephrotoxicity; non-opioid analgesic; novel; novel marker; overexpression; renal damage; repaired; synthetic cannabinoid; urinary

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.

项目摘要 尽管大麻用于医疗或娱乐用途广泛合法化， 尽管大麻产业的产值高达数十亿美元，但大麻对健康的影响却没有得到充分的描述。 实验证据支持大麻素系统在几种形式的慢性炎症中的致病作用。 肾脏疾病（CKD）和病例系列揭示了合成大麻素使用与 急性肾损伤（阿基）。然而，缺乏流行病学证据表明， 大麻对肾脏健康的影响以前的队列研究受到大麻评估不足的限制 暴露，大麻使用者中的低暴露水平，或对肾脏健康结果的不完整评估。 随着向公众大规模销售大麻，扩大了高效力大麻产品的供应， CKD患者的疼痛管理选择不足，评估其潜在的 大麻的肾毒性或安全性。 该提案将调查大麻使用对心脏和大麻（THC）肾脏健康的影响。 一项当代和国家大麻使用者（N= 1，132）和非使用者（N= 2，863）队列研究， 冠状动脉疾病作为一个出生队列设计，THC研究已经确定了当前和终身 通过电话健康访谈，所有参与者的大麻暴露，超过99%的参与者 同意后续联系进行研究随访。与此同时， 记录和住院诊断的临床结果，THC研究提供了前所未有的 我们提议的肾脏健康调查的机会。第一个目标将评估 大麻暴露与慢性肾脏病的风险和肾功能的纵向变化超过五年。第二 Aim将在五年内研究大麻暴露与阿基风险的关系。最后，第三个目标将 探索大麻在基线和一年后的亚临床肾毒性，使用一组尿 生物标志物捕获肾脏健康的五个不同组成部分：肾小球损伤;肾小管功能障碍;肾小管 损伤;小管炎症和纤维化;以及小管修复和储备。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诱导的肾毒性中的效用。这些 这些项目将：1）提供关于大麻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）为以下方面奠定基础 未来的研究可以评估基于生物标志物的策略，以监测大麻对人体的肾毒性 CKD的风险。