Recently reported genetic evidence suggests that previously observed associations between higher coffee and caffeine intake and lower kidney stone risk are causal.

“Increasing coffee and caffeine consumption may be a prevention strategy for kidney stones,” investigators Shuai Yuan, BMed, and Susanna C. Larsson, PhD, of Karolinska Institutet in Stockholm, Sweden, concluded in a paper published in the American Journal of Kidney Diseases.

The study used a Mendelian randomization design, an approach that “can minimize residual confounding because genetic variants are randomly allocated at conception and thus generally unrelated to confounders, such as environmental and self-adopted factors,” the investigators explained.

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From previously published meta-analyses, the investigators selected independent genetic variants associated with coffee and caffeine consumption at the genome-wide significance level. They obtained kidney stone data from the UK Biobank study (6436 cases and 388,508 noncases) and the FinnGen consortium (3856 cases and 172,757 noncases).

A genetically predicted 50% increase in coffee consumption was significantly associated with 40% decreased odds of kidney stone formation, according to the investigators. A genetically predicted 80-mg increase in caffeine consumption was significantly associated with 19% decreased odds of kidney stones.

“Along with previous traditional epidemiological data, these findings suggest that coffee and caffeine consumption may prevent kidney stone disease,” Drs Yuan and Larsson wrote.

They discussed underlying mechanisms for the inverse associations between coffee and caffeine consumption and kidney stones. Caffeine is a diuretic, so the caffeine in coffee, when adequately compensated by water intake, results in increased urine flow, an important protective factor against kidney stone development, they explained. Caffeine can also decrease adhesion of calcium oxalate crystals on the apical surface of renal tubular epithelial cells.

“The elegant design of this study, which takes advantage of genetic variants associated with higher coffee and caffeine consumption, strengthens the evidence that coffee and caffeine can prevent kidney stones,” Kerry Willis PhD, Chief Scientific Officer for the National Kidney Foundation, said in a statement. “Given the increasing prevalence of kidney stones in the United States and the associated morbidity, it would be great if this turns out to be a new prevention strategy that is both accessible and affordable.”

Findings from the new study support those of some observational studies, such as a cohort study of 194,095 participants. On multivariate analysis, individuals who consumed 1 or more servings per day of caffeinated coffee had a 26% lower risk for kidney stones compared with those who consumed less than 1 serving per week, the investigators reported in the Clinical Journal of the American Society of Nephrology. The study had a median follow-up duration of more than 8 years.


Yuan S, Larsson SC. Coffee and caffeine consumption and risk of kidney stones: A Mendelian randomization study. Am J Kidney Dis. Published online October 21, 2021. doi:10.1053/ j.ajkd.2021.04.018

Ferraro PM, Taylor EN, Gambaro G, Curhan GC. Soda and other beverages and the risk of kidney stones. Clin J Am Soc Nephrol. 2013;8:1389-1395. doi:10.2215/CJN.11661112