In a recent article published in nutrientsresearchers evaluated the relationship between coffee consumption and genetic predisposition to caffeine metabolism on kidney function.
Caffeinated beverages such as coffee and tea are widely consumed worldwide. Caffeine is also present in everyday life in energy drinks, sodas and analgesics.
Given the increasing prevalence of kidney disease, researchers postulate that increased caffeine consumption has adverse effects on kidney structure and function. However, the exact effects of caffeine intake on kidney function remain unclear.
Experimental studies using animal models indicate that caffeine consumption increases renal vascular resistance and proteinuria, leading to renal failure.
Similarly, human studies suggest that in patients with polycystic kidney disease (PKD), caffeine intake may increase the risk of cyst enlargement compared to those who do not consume caffeine. However, data from observational studies appear to be skewed due to the design and assessment methods used.
About the research
In the ongoing Mendelian Randomization (MR) study, researchers obtained summary genetic association statistics for plasma caffeine levels and caffeine intake from meta-analyses of genome-wide association studies (GWAS) covering 9,876 and >47,000, respectively the individual of European origin.
Previous GWAS conducted in people of European descent have shown that cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AHR) genes are associated with caffeine metabolism. CYP1A2 metabolizes more than 95% of caffeine in humans, and AHR regulates its expression.
Thus, in this study, the researchers adopted a two-sample MR approach to analyze single nucleotide polymorphisms (SNPs) within a 100-kilobase window of CYP1A2 and AHR gene regions. Specifically, they selected the strongest signal at each locus, specifically rs242297 and rs4410790, respectively.
They examined these effects on kidney function, including estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine sodium, albumin-to-creatinine ratio (UACR), and risk of chronic kidney disease (CKD).
Finally, they pooled the estimates for both genetic instruments using the random-effects weighted inverse variance method to derive Wald ratios with MR standard errors.
Adopting an MR approach helped researchers overcome limitations of observational methods, including biases due to environmental factors and reverse causation and selection of genes encoding enzymes with established roles in caffeine metabolism. Genetic tools minimized the pleiotropic effects of the MR design in this study.
Consistent with experimental studies, higher genetically predisposed plasma levels of caffeine showed an adverse effect on eGFR measurements determined using creatinine or cystatin C.
Conversely, a higher genetic predisposition to caffeine intake exerted a protective effect on renal function. Increases eGFR and reduces the risk of CKD. According to the authors, the observed discrepancy is likely due to rapid caffeine metabolizers requiring greater caffeine intake to achieve the same psychostimulant effect as slow metabolizers.
In addition, higher genetically predicted plasma caffeine levels showed adverse associations with two biological markers of CKD progression, urinary sodium and BUN, but not UACR. However, the researchers found no evidence of any deleterious effect of genetically predicted plasma caffeine levels on albuminuria.
The CKDGen GWAS consortium selected 25 SNPs, including those examined in this study, and found that an additional cup of coffee per day provided a protective effect against CKD, an important finding that should be incorporated into future studies.
To summarize, the present MR study demonstrated that coffee consumption and genetic predisposition to caffeine metabolism have opposite effects on renal function, with the former having a protective effect and the latter having a deleterious effect on renal function.
However, the present study could not determine whether the observed effects on renal function were due to the adverse effects of higher plasma caffeine levels or to the protection afforded by greater consumption of caffeinated beverages; therefore, future studies should investigate the same.