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More Good News: Coffee Prevents Kidney Stones

  • Pietro Manuel Ferraro
    Correspondence
    Address for Correspondence: Pietro Manuel Ferraro, MD, MSc, PhD, U.O.C. Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168, Roma, Italia.
    Affiliations
    U.O.S. Terapia Conservativa della Malattia Renale Cronica, U.O.C. Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
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  • Gary C. Curhan
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Published:October 21, 2021DOI:https://doi.org/10.1053/j.ajkd.2021.07.002
      Related Article, p. 9
      Kidney stone disease is increasingly common in the general population; recent estimates suggest a prevalence higher than 10% in the United States.
      • Chen Z.
      • Prosperi M.
      • Bird V.Y.
      Prevalence of kidney stones in the USA: The National Health and Nutrition Evaluation Survey.
      To reduce the burden and associated high costs for health systems,
      • Saigal C.S.
      • Joyce G.
      • Timilsina A.R.
      Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management?.
      a large body of literature has focused on modifiable risk factors, especially dietary, thought to play a role in the pathogenesis of the disease.
      • Ferraro P.M.
      • Taylor E.N.
      • Gambaro G.
      • Curhan G.C.
      Dietary and lifestyle risk factors associated with incident kidney stones in men and women.
      However, given the time and large expense required to perform a randomized controlled trial, most of the available evidence on the benefit or harm of certain dietary factors derives from observational studies, which—depending on the study design—could be potentially subject to issues such as reverse causation or residual confounding. To overcome this limitation and derive causal estimates without an expensive trial, a technique called Mendelian randomization (MR) has been devised, which takes the random allocation of genes at conception and uses them as instrumental variables to explore the causal association between an exposure and an outcome. When the assumptions of MR hold, estimates obtained with this technique can be regarded as causal and unbiased estimates of the true association of interest.
      • Sekula P.
      • Del Greco M.F.
      • Pattaro C.
      • Köttgen A.
      Mendelian randomization as an approach to assess causality using observational data.
      Previous studies have consistently reported an inverse association between intake of coffee
      • Ferraro P.M.
      • Taylor E.N.
      • Gambaro G.
      • Curhan G.C.
      Soda and other beverages and the risk of kidney stones.
      ,
      • Littlejohns T.J.
      • Neal N.L.
      • Bradbury K.E.
      • Heers H.
      • Allen N.E.
      • Turney B.W.
      Fluid intake and dietary factors and the risk of incident kidney stones in UK Biobank: a population-based prospective cohort study.
      and caffeine
      • Ferraro P.M.
      • Taylor E.N.
      • Gambaro G.
      • Curhan G.C.
      Caffeine intake and the risk of kidney stones.
      and the risk of incident kidney stones, suggesting a protective role for those factors. In this issue of AJKD, Yuan and Larsson
      • Yuan S.
      • Larsson S.C.
      Coffee and caffeine consumption and risk of kidney stones: a Mendelian randomization study.
      apply the MR approach to evaluate the potential causal association between intake of coffee and caffeine and development of kidney stones.
      Yuan and Larsson used publicly available data and selected 12 single-nucleotide polymorphisms (SNPs) associated with coffee consumption and 2 SNPs associated with caffeine consumption from meta-analyses of specific genome-wide association studies (GWAS) performed on individuals of European ancestry. Overall, the selected instruments only explained up to 1.3% of the variance in intake, but this is in line with previous MR analyses. Coffee and caffeine consumption were estimated through food frequency questionnaires. Betas and standard errors for the association between those SNPs and kidney stones (defined by ICD codes) were obtained from GWAS performed on 2 independent cohorts, the UK Biobank and the FinnGen Consortium. Using the inverse-variance weighted method, the authors computed causal estimates for coffee intake (40% lower odds of stones for a 50% increase in intake, corresponding to an increase from 1 to 1.5 cups per day) and caffeine intake (19% lower odds of stones for an 80 mg increase in intake, corresponding to 1 additional cup of caffeinated coffee), thus confirming the protective effect suggested by previous studies.
      This well-conducted study raises several points of discussion. First, confirming and strengthening previous consistent observational findings makes a randomized controlled trial on this particular topic appear unnecessary, thus saving resources for generating evidence for other questions. The study is also an example of the wealth of information that can be obtained from studies combining detailed phenotyping with “omics” data, such as the UK Biobank study; there is no doubt that such studies will be instrumental in improving our understanding of complex, noncommunicable diseases. Nonetheless, each study design has its own inherent limitations. Whereas the MR approach minimizes the distortion due to reverse causation and residual confounding that are common in cross-sectional studies, its advantages over well-designed, large, longitudinal cohort studies with rigorous assessment of exposures and outcomes are often minimal, as supported by the fact that the estimates obtained by Yuan and Larsson with the MR approach largely overlap with those obtained from such studies. Of note, the MR approach, by treating each exposure with its own set of instrumental variables, is less flexible than a cohort study with participant-level information in studying the independent associations of multiple exposures. For instance, in our previous work we were able analyze the risk profile of noncaffeinated coffee
      • Ferraro P.M.
      • Taylor E.N.
      • Gambaro G.
      • Curhan G.C.
      Soda and other beverages and the risk of kidney stones.
      as well as of caffeine from noncoffee sources,
      • Ferraro P.M.
      • Taylor E.N.
      • Gambaro G.
      • Curhan G.C.
      Caffeine intake and the risk of kidney stones.
      which would not be feasible with an MR approach.
      In conclusion, the integration of high-quality observational studies, MR approaches, multi-omics data, and interventional studies will be the key to expand our understanding of the pathogenesis of kidney stone disease and thus to deliver the best possible care for the patient. The new data from the study by Yuan and Larsson combined with the compelling observational data should put to rest the old and incorrect misconception that coffee is dehydrating and should be avoided by kidney stone formers. In fact, this study provides causal evidence that coffee and caffeine reduce the risk of kidney stones.

      Article Information

      Authors’ Full Names and Academic Degrees

      Pietro Manuel Ferraro, MD, MSc, PhD, Gary C. Curhan, MD, ScD.

      Support

      None.

      Financial Disclosure

      Dr Ferraro received consultant fees and grant support from Allena Pharmaceuticals, Alnylam, AstraZeneca, BioHealth Italia, Vifor Fresenius, and royalties as an author for UpToDate. Dr Curhan is an employee of OM1, Inc, has received consulting fees from Allena Pharmaceuticals, and receives royalties as a Section Editor and author for UpToDate.

      Peer Review

      Received July 3, 2021 in response to an invitation from the journal. Accepted July 4, 2021 after editorial review by an Associate Editor and a Deputy Editor.

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