Study finds no evidence of causal effect between CKD, cannabis
Click Here to Manage Email Alerts
According to data published in Kidney Medicine, there is no evidence that cannabis use causes chronic kidney disease, and researchers of the study suggest CKD should not be a limiting factor for cannabis use.
“Cannabis is likely the most-used recreational substance after alcohol and nicotine. [More than] 50% of U.S. adults have used it at least once in life, and many countries have now legalized its use. Nonetheless, multiple drugs acting on cannabinoid signaling are in clinical development. Thus, we thought it was relevant to assess cannabis impact on human health and in particular in nephrology, our area of expertise,” Sergio Dellepiane MD, PhD, nephrology translational lead of the Technology and Translational Research Team at Genentech, and Ishan Paranjpe, MD, BS, internal medicine resident physician at Stanford University, told Healio. “However, available studies have several biases; mainly because of the social stigma associated with the use of recreational substances, that directly reflects on data quality. Thus, we decided to use a different approach. As a first step, we observed a positive association between cannabis use and CKD by analyzing the largest sample investigated so far. Subsequently, we tried to assess causality with a Mendelian randomization [MR].”
Method
In a retrospective cohort study and genome-wide association study, researchers evaluated data of 223,354 participants from the All of Us cohort to determine the relationship between CKD and cannabis use. Participants completed surveys to detail the frequency of cannabis use and were categorized based on previous 3-month consumption as no users, current users who used cannabis less than monthly, those who used monthly, those who used weekly and those who used daily. According to the authors, the survey did not differentiate between different types of cannabis consumed.
With cannabis consumption serving as the exposure, researchers considered CKD outcomes, such as cystatin-C and creatinine-based kidney function, proteinuria and blood urea nitrogen, as primary outcomes of the study.
Using association analyses, researchers examined frequency of cannabis use and CKD. Further, researchers conducted a two-sample MR to measure casual association.
“MR identifies genetic predispositions to a risk factor (like cannabis use) and associates them to an outcome (in this case, CKD). There are specific conditions to be met for this kind of analysis but, in few words, it mimics a randomized clinical trial,” Dellepiane and Paranjpe told Healio. “Indeed, based on Mendelian laws of genetics, gene variants are randomly distributed in the population and can be assimilated to a chronic exposure to the studied risk factor. Compared to standard observational studies, this technique is stronger in causal inference.”
Results
A total of 80,132 participants reported lifetime cannabis use, none of which were significantly associated with CKD when adjusted for covariates. Additionally, those who used cannabis less than monthly and those who used it monthly did not have higher odds of prevalent CKD when compared with former users.
Although, weekly and daily use significantly correlated with CKD, researchers noted this is most likely due to reverse causation given chronically ill patients are more likely to use cannabis.
“In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD,” the researchers wrote in their study, finding an OR of 1 for this outcome.
“For sure, there remains multiple unanswered questions, including the differential effects of the two cannabinoid receptors on kidney tissue and the nuances among the different substances,” Dellepiane and Paranjpe told Healio. “However, the knowledge that is building up from different teams seems to consolidate behind the same message: Cannabis may not be harmful for the kidneys.”
In this study, there was likely under reporting of cannabis use. Additionally, the genetic instruments used in the MR consisted of many individuals of European ancestry.
Dellepiane and Paranjpe said, “Keeping in mind the limitations of our study, we suggest that CKD should not be considered a limiting factor for the use of cannabis. This could positively affect specific patient groups that might benefit from cannabis effects on pain, appetite, nausea or the other indications that are under investigation.”
Collapse
Read more about
Click Here to Manage Email Alerts