Critique #277 – Association between drinking status and risk of kidney stones among United States adults: NHANES 2007–2018
Title
Association between drinking status and risk of kidney stones among United States adults: NHANES 2007–2018
Authors
Wei B; Tan W; He S; Yang S; Gu C; Wang S
Citation
BMC Public Health (2024) 24, 820. https://doi.org/10.1186/s12889-024-18307-1
Author’s Abstract
Objective This study aimed to investigate the relationship between drinking status and kidney stones occurrence among United States (US) adults who consume alcohol.
Methods We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES 2007–2018). Questionnaires yielded information on alcohol consumption and kidney health. Drinking status was categorized into four groups—former, mild, moderate, and heavy—based on alcohol consumption patterns. The aim was to explore the relationship between drinking status and the prevalence of kidney stones occurrence. For this analysis, we examined a group of individuals diagnosed with kidney stones. With survey weights applied, the total weight of the group was 185,690,415.
Results We used logistic regression to measure the relationship between drinking status and the likelihood of developing kidney stones. In a fully adjusted model, former drinkers were less likely to have previously experienced kidney stones (OR 0.762, 95% CI 0.595–0.977, P < 0.05). In subgroup analysis, heavy alcohol consumption was associated with a significantly reduced likelihood of kidney stones occurrence in various populations. The adjusted odds ratios (with 95% confidence intervals) of kidney stones risk for heavy alcohol consumption were 0.745 (0.566–0.981) for young individuals, 0.566 (0.342–0.939) for older individuals, 0.708 (0.510–0.981) for individuals of white race, 0.468 (0.269–0.817) for individuals with underweight/normal BMI, 0.192 (0.066–0.560) for widowed people, 0.538 (0.343–0.843) for smoking individuals, 0.749 (0.595–0.941) for individuals without a cancer history, and 0.724 (0.566–0.925) for individuals without a stroke history.
Conclusions In US adults who consume alcohol, a negative linear relationship is apparent between drinking status and the prevalence of kidney stones, with heavy drinking showing a lower prevalence compared to former drinkers. However, the causal relationship between drinking status and kidney stones requires further investigation in future research endeavours.
Forum Summary
ISFAR has previously reported on the association between drinking status and kidney chronic disease and kidney cancer, which collectively suggest that moderate alcohol consumption may have an overall beneficial effect on kidney health. Kidney stone formation may be predictive of developing either chronic kidney disease or kidney cancer, where renal stone formers have twice the risk of chronic kidney disease. In this study by Wei et al. (2024), a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES 2007–2018), also suggests that heavy alcohol consumption may reduce the likelihood of kidney stones occurrence.
Forum Comments
Background
Chronic kidney disease (CKD) is a disease characterized by progressive damage and loss of function in the kidneys. CKD affects more than one in seven US adults—an estimated 37 million Americans (Abufaraj et al., 2021). In Europe, 100 million people suffer from CKD and predictions suggest that it will become the fifth leading cause of death globally by 2040. In addition, CKD is among the most expensive diseases for health systems, with a cost estimated at EUR 140 billion annually in Europe[1]. Worldwide, the ESKD incidence rate is approximately 1.5 times as high for males than females and increases with age for both males and females, being highest for those aged 75 and over. In addition, in Australia, the age-standardized ESKD incidence rate for Indigenous people was five-times the rate for non-Indigenous people (AIHW 2018).
Early-stage kidney disease (ESKD) usually has no symptoms, and many people do not know they have CKD until it is very advanced. Kidney disease often gets worse over time and may lead to kidney failure and other health problems, such as stroke or heart attack. Nearly 808,000 people in the USA are living with end-stage kidney disease—kidney failure that is treated with a kidney transplant (31%) or dialysis (69%)[2]. The two most common causes of kidney disease are diabetes and high blood pressure. Other risk factors for developing kidney disease include heart disease, obesity and a family history of kidney failure[3].
Recent observational studies have shown that renal cell carcinoma (RCC) risk is increased about three-fold in ESKD (Brooks et al., 2023). Lower estimated glomerular filtration rate (eGFR) is independently associated with a higher risk of renal cancer (Lowrance et al., 2014). This suggests that kidney disease exerts a specific, localized carcinogenic effect on kidney cells (Weng et al., 2011).
ISFAR previously reported on the associations between drinking status and kidney cancer[4] and chronic kidney disease[5]. The oldest critique, #85, reported on a meta-analysis of the association between moderate alcohol consumption and a lower risk of kidney cancer based on a study in 2012 (Song et al., 2012). This inverse association was confirmed in a recent meta-analysis on a larger number of food groups and urologic cancer risk (Qi et al., 2023). Another more recent ISFAR critique, #225, reported on a study showing that moderate alcohol consumption was associated with a lower risk of chronic kidney disease (Hu et al., 2020), a finding that was recently confirmed in a dose-response meta-analysis (Yuan et al., 2021). These findings suggest that moderate alcohol consumption may have an overall beneficial effect on the kidneys as has been shown for the cardiovascular system.
Kidney (renal) stones or nephrolithiasis are an important cause of CKD and ESKD. Renal stone formers have twice the risk of CKD or ESKD (Gambaro et al., 2017). Also, kidney stones may increase the risk of renal cell carcinoma in men and may increase the risk of transitional cell carcinoma (Cheungpasitporn et al., 2015).
This critique concerns the recent study focusing on the association between drinking status and risk of kidney stones in the USA (Wei et al., 2024). This study helps further explain the beneficial relation between moderate alcohol consumption and CKD, since kidney stones are a risk factor not only for CKD and ESKD but also for renal cell cancer.
This cross-sectional analysis showed that participants, who had previously passed at least one kidney stone, and were mild, moderate or heavy alcohol consumers had lower odds of developing stones compared to former drinkers. Full adjustment for all covariables attenuated the association and only the heavy drinkers remained associated with a 24% reduction in nephrolithiasis.
By the way, we believe that the second sentence of the results section of the abstract was incorrect. It should read: In a fully adjusted model, heavydrinkers were less likely to have previously experienced kidney stones (OR 0.762, 95% CI 0.595–0.977, P < 0.05).
Critique
This study by Wei et al. (2024) is interesting and not new. A previous study using 303 participants attending hospital with a new kidney stone episode also showed that moderate alcohol consumers had a reduced risk for kidney stone formation along with those that were ‘moderate or low-meat eaters’ (50-99 g/day and <50 g/day, respectively), fish-eaters and vegetarians. Also, other dietary factors such as fibre, fresh fruit and whole grain cereals, conferred some protection, showing that dietary factors are important, either directly or indirectly through known risk factors such as diabetes, hypertension and obesity. Similarly, other studies; a longitudinal study from the UK (Littlejohns et al., 2020), and a case-control study from Korea (Kim et al., 2022) reported similar findings, whereas other studies did not find such an association. However, a meta-analysis and a dose-response relationship analysis did show that the rate of urolithiasis decreased by 10% for a 10 g/day increase in alcohol intake (Wang et al., 2015).
Yet another meta-analysis performed in 2015 (Xu et al., 2015) showed that each 500 mL increase in water intake was associated with a significantly reduced risk of kidney stone formation with protective associations for higher intakes of tea and alcohol. The author concluded that increased water intake is associated with a reduced risk of kidney stones, whereas increased consumption of tea and alcohol may reduce kidney stone risk. This means that it is unclear whether the beneficial association between alcohol consumption and kidney stones is mediated by the intake of specific ingredients in alcoholic beverages or that fluid intake in general is the main contributing factor. The latter may be supported by the observation that the primary risk factor for stone formation is low urine output (Cheungpasitporn et al., 2016).
Wei et al. (2024) used a number of models to correct for confounding factors. Models #3 and #4 included correction for BMI, diabetes and heart attacks, whereas these diseases are also risk factors for kidney stones. The authors report that no associations were observed between drinking and kidney stones in individuals with diabetes or heart attack and that no significant interaction effects occurred after adjusting for these covariates. It would have been nice to confirm the effects of established risk factors on the associations between these risk factors and the incidence of kidney stones.
Also, no potential mediating biomarkers were evaluated in this study. It may have been interesting to see the associations of these potential mediating factors like HDL cholesterol, apolipoprotein A1 and adiponectin to try and shed more light on the potential mechanisms that may underly reduced nephrolithiasis. The potential mediators mentioned by the authors were cardiovascular disease, diabetes and inflammatory risk factors, however, the relationship between these risk factors and calcium oxalate stone formation is unclear.
Alternatively, acetate formation formed during ethanol metabolism may also be interesting to investigate. A recent animal study suggests that it may prevent kidney stone formation. For example, rats fed vinegar had reduced renal calcium oxalate stones by regulating acetate metabolism in gut microbiota (Liu et al., 2022). Understanding possible mechanisms of action in addition to an epidemiological association may be extremely valuable.
Altogether, the associations between alcohol consumption and kidney stones, chronic kidney disease, and renal cell carcinoma suggest that the kidney is yet another organ, as is the cardiovascular system, that may be beneficially affected by alcohol consumption.
Specific Comments from Forum Members
Forum member Waterhouse considers that “this study does not appear to reveal much new information and the number of uncorrected typos suggest the authors were not very engaged in the writing. In addition, they did not appear to apply much thought to the investigation. As for typos, you have already noted a key error in the abstract, and one sentence (p6) says: “However, findings from one Guangzhou hospital revealed no significant differences in alcohol consumption between never drinkers, occasional drinkers, and regular drinkers, as well as beer, wine, and hard liquor consumption [cite].” As for limitations of their investigation, there are many reports that total water or fluid intake affects kidney stones, and they mention some of those studies, but they did not bother to pull that data on this population. I find it frustrating that they state the aim of their study is “understanding the potential association between drinking status and kidney stones development better”, but they do not reveal anything new at all, and they conclude that a causal relationship needs further investigation”.
Forum member Harding states that he “too wondered why the authors appear to give equal weight to studies drawing on large databases or meta-analyses on the one hand, and the findings from one hospital (Reference #14) on the other. I have looked at the studies they cite that conclude alcohol consumption is protective (References #7 to 10), and those that do not (References #11 to14). I have only managed to find the abstract for Reference #7, but it does not seem to involve alcohol at all. Reference # 8 is a large Korean study of over 28,000 patients, and Reference #9 is a meta-analysis. Reference #10 drew on UK Biobank data. Of those cited that did not find a protective effect (‘inconsistencies’), Reference #11 is a study of twins in Vietnam and in the discussion (p.1059), the authors say, ‘In our analysis, alcohol consumption was protective, and there was an increased prevalence of stones among current non-drinkers’. I have only seen the abstract of Reference #12 (Hall et al), but based on it, I wonder whether alcohol consumption was actually recorded. In Reference #13 (Liu et al), the authors say, ‘This study did not find a significant association between alcohol consumption and risk of calcium urolithiasis’ (i.e. neither one way nor the other) but the sample size was small (354 cases). Reference #14 (Zhao et al) is based on 725 cases and used a food frequency questionnaire to determine alcohol intake. There were only two categories – non-drinkers, and current drinkers (those consuming three or more drinks a month), so it is hard to see how any solid conclusions can be drawn from that. So, after looking at References #11 to 14, I don’t see that considered together they can be used to justify that alcohol consumption is not protective for kidney stones.”
Forum member Skovenborg suggests, in addition, that “Reference #7 did not investigate or mention alcohol, and while Reference #12 did investigate alcohol intake, the intake of both cases and controls was similar and very low. Problems with references are ‘more the rule than the exception’ in my experience. I have often asked the authors to comment on some examples of inconsistency, but I never received an answer. These flaws should have been picked up at the peer review in theory…”
Concluding comments
Forum member Ellison concludes that “over many decades, epidemiologic studies have consistently shown that abnormal renal function, and even renal tumours, are less common among drinkers than among non-drinkers. I do not believe that all reasons for this protective effect are known. While the present study does not add much to learning about mechanisms, it does add to the evidence that drinking may have a favourable effect on the risk of many forms of renal dysfunction.”
References
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Australian Institute of Health and Welfare 2018. Australia’s health 2018. Australia’s health series no. 16. AUS 221. Canberra: AIHW
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Cheungpasitporn, W., Thongprayoon, C., O’Corragain, O. A., Edmonds, P. J., Ungprasert, P., Kittanamongkolchai, W., & Erickson, S. B. (2015). The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis. QJM : Monthly Journal of the Association of Physicians, 108(3), 205–212. https://doi.org/10.1093/qjmed/hcu195
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Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:
Henk Hendriks, PhD, Netherlands
Creina Stockley, PhD, MBA, Independent consultant and Adjunct Senior Lecturer in the School of Agriculture, Food and Wine at the University of Adelaide, Australia
Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark
Richard Harding, PhD, Formerly Head of Consumer Choice, Food Standards and Special Projects Division, Food Standards Agency, UK
R. Curtis Ellison, MD, Section of Preventive Medicine/Epidemiology, Boston University School of Medicine, Boston, MA, USA
Andrew Waterhouse, PhD, Department of Viticulture and Enology, University of California, Davis, USA
Giovanni Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy
Mladen Boban, MD, PhD, Professor and Head of the Department of Pharmacology, University of Split School of Medicine, Croatia
Ramon Estruch, MD, PhD. Associate Professor of Medicine, University of Barcelona, Spain
Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, University of Arizona School of Medicine, Tucson, AZ, USA
Pierre-Louis Teissedre, PhD, Faculty of Oenology–ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France
Monika Christmann, PhD, Head of Institute, Department of Enology and Professorship for Enology, Hochschule Geisenheim University, Germany
[1] https://www.europarl.europa.eu/doceo/document/O-9-2022-000006_EN.html#:~:text=In%20Europe%2C%20100%20million%20people,140%20billion%20annually%20in%20Europe.
[2] https://usrds-adr.niddk.nih.gov/2022
[3] https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease
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