Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study.

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de La Harpe, Roxane  ORCID logo
Cronje, Héléne T 

Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease.


Peer reviewed: True

Publication status: Published

Mendelian randomization, caffeine intake, caffeine level, causal inference, estimated glomerular filtration rate, genetically predicted coffee consumption, kidney function, Humans, Caffeine, Mendelian Randomization Analysis, Genome-Wide Association Study, Kidney, Renal Insufficiency, Chronic, Polymorphism, Single Nucleotide
Is Part Of
British Heart Foundation Centre of Research Excellence (RE/18/4/34215)
Swedish Heart Lung Foundation (20210351)
Swedish Research Council for Health, Working Life and Welfare (2018-00123)
Swedish Research Council (2019-00977)
Swedish Cancer Society (Cancerfonden)