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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要尽管大麻的药用或娱乐用途广泛合法化，并且大麻的开发尽管大麻产业价值数十亿美元，但大麻对健康的影响尚未得到充分表征。实验证据支持大麻素系统在多种形式的慢性疾病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肾病风险之间的联系急性肾损伤（AKI）。然而，缺乏关于其影响的流行病学证据。大麻对肾脏健康的影响。之前的队列研究因对大麻的评估不充分而受到限制接触、大麻使用者接触水平低或肾脏健康结果评估不完整。随着向公众大规模营销大麻，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，因此评估潜在的疼痛管理选择至关重要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。 THC 研究以出生队列为设计对象，已确定当前和一生通过电话健康访谈了解所有参与者的大麻暴露情况，超过 99% 的参与者同意随后联系以进行研究跟进。连同队列获得电子健康的机会 THC 研究提供了前所未有的临床结果记录和住院诊断我们提出的肾脏健康调查的机会。第一个目标将评估以下关联五年内暴露于大麻会导致慢性肾病（CKD）风险和肾功能纵向变化。第二个 Aim 将研究五年内接触大麻与 AKI 风险的关联。最后，第三个目标将使用一组尿液研究在基线和一年后探索大麻的亚临床肾毒性捕获肾脏健康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;小管受伤;肾小管炎症和纤维化；以及，肾小管修复和储备。我们的调查团队拥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方面的实用性。这些项目将： 1）提供有关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； 3）奠定基础未来的研究可以评估基于生物标记的策略来监测大麻对人体的肾毒性有 CKD 风险。