Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

RATIONALE & OBJECTIVE: The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS).

STUDY DESIGN

Retrospective cohort study and genome-wide association study.

SETTING & PARTICIPANTS: The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million).

EXPOSURE

Cannabis consumption.

OUTCOMES

CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen.

ANALYTICAL APPROACH

We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization.

RESULTS

In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18;  = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52;  = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60;  = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50;  = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01;  = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits.

LIMITATIONS

Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry.

CONCLUSIONS

Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.