Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization

Sergio Dellepiane; Ishan Paranjpe; Madhumitha Rajagopal; Samir Kamat; Ross O'Hagan; Faris Gulamali; Joshua L Rein; Alexander W Charney; Ron Do; Steven Coca; Benjamin S Glicksberg; Girish N Nadkarni

doi:10.1016/j.xkme.2022.100582

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization

Kidney Med. 2022 Dec 11;5(2):100582. doi: 10.1016/j.xkme.2022.100582. eCollection 2023 Feb.

Authors

Sergio Dellepiane^{1

2

3}, Ishan Paranjpe^{1

2}, Madhumitha Rajagopal¹, Samir Kamat^{1

2}, Ross O'Hagan^{1

2}, Faris Gulamali^{1

2}, Joshua L Rein³, Alexander W Charney^{1

4

5

6}, Ron Do^{4

7}, Steven Coca^{2

3}, Benjamin S Glicksberg^{1

2

4}, Girish N Nadkarni^{1

2

3

7

8}

Affiliations

¹ Mount Sinai Clinical Intelligence Center (MSCIC), Icahn School of Medicine at Mount Sinai, New York, NY.
² Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY.
³ Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY.
⁴ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
⁵ Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY.
⁶ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷ Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
⁸ Department of Medicine, Division of Data Driven and Precision Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Abstract

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; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 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; P = 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.

Keywords: Cannabis; Mendelian randomization; chronic kidney disease.

Grants and funding

UL1 TR004419/TR/NCATS NIH HHS/United States