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.
Cannabis use is increasingly common but its risks and benefits have not been well studied. This proposal will investigate whether or not cannabis use increases the risk of kidney damage in persons with heart disease. The knowledge gained will help patients and clinicians better understand the effects of cannabis on kidney health, and may reduce the burden of kidney disease among millions of individuals worldwide.
