Water Intake and Risk of Kidney Stone
Nine studies27,30,31,33–38 reported on the association between water intake and risk of kidney stones, with 3 of the studies33,34,38 being multiple publications of study.35 All of these studies included dose–response data. The combined RR for every 500 mL increment of water intake (linearity) a day was 0.93 (95% CI: 0.87, 0.98; P < 0.01; Figure 2). Substantial heterogeneity (I2 = 78.3%, P < 0.01) was detected among studies. Little evidence of nonlinear association was detected (P for nonlinearity test = 0.22). When using 1500 mL of daily water intake as the inference dose (RR = 1), the RRs of kidney stones for 1000 mL (approximate), 2000, 2500, and 3100 mL were 1.07 (95% CI: 1.05, 1.09), 0.92 (95% CI: 0.89, 0.95), 0.84 (95% CI: 0.78, 0.91), and 0.74 (95% CI: 0.65, 0.86), respectively.
Coffee Consumption and Risk of Kidney Stones
Seven studies6,29,30,36,38–40 investigated the relationship between coffee consumption and risk of kidney stones (Table 1). Two studies6,40 were identified as multiple publications of study.38 From the remaining 5 studies, three30,38,39 reported dose–response relationship information, while two29,39 did not. Our meta-analysis showed that, compared to no coffee consumption, drinking 1 to 2 cups (about 110–240 mL) of coffee a day was associated with a RR of kidney stones of 0.88 (95% CI: 0.76, 1.00; P = 0.05; Figure 3). Moderate heterogeneity (I2 = 54.7%) was detected among studies. In dose–response meta-analysis, the RR for every 110 mL increment of coffee intake was 0.90 (95% CI: 0.87, 0.93; P < 0.01), and the Wald test showed nonsignificant of nonlinearity (P = 0.77).
Tea Consumption and Risk of Kidney Stones
Nine studies6,28,29,30,31,36,38–40 reported data on the association between tea consumption and kidney stones. Studies6,40 were identified as the same publication of study.38 After excluding multiple publications, 3 studies reported dose–response information.30,38,39 The meta-analysis showed that, compared to no tea consumption, those who consumed 1 to 2 cups of tea per day had a RR of kidney stones of 1.06 (95% CI: 0.94, 1.20; P = 0.32; I2 = 45.5%; Figure 4). When modeled as a continuous variable, each 110 mL/day increase in tea consumption was associated with a kidney stone RR of 0.96 (95% CI: 0.93, 0.99; P = 0.02), and there was some evidence this relationship was borderline nonlinear (P = 0.07 for nonlinearity test). The protective effect of tea consumption appeared to begin at an intake level of approximately 250 mL/day. Compared to the reference dose (0 mL), those whose daily tea intake was 102, 204, 257, 525, and 825 mL, had a RR of kidney stones of 1.02 (95% CI:0.95, 1.09), 0.97 (95% CI: 0.90, 1.04), 0.91 (95% CI: 0.86, 0.99), 0.59 (95% CI: 0.39, 0.89), and 0.33 (95% CI:0.13, 0.84), respectively.
Alcohol Intake and Risk of Kidney Stones
Nine studies6,18,27,29,30,36,38–40 with 7 of the studies being unique,18,27,29,30,36,38,39 reported on the association between alcohol intake and risk of kidney stones. Of these studies,18,30,36,38 reported dose–response information. Studies6,40 were identified as the same publication of study.38 The meta-analysis showed that, compared to those who did not drink alcohol, those who drank about 1 standard drink (12 g) of alcohol per day had a RR of kidney stones of 0.80 (95% CI: 0.63, 1.01; P = 0.06; I2 = 67.1%; Figure 5). When modeled as a continuous variable, each 10 g/day increase in alcohol consumption was associated with a kidney stone RR of 0.80 (95% CI: 0.75, 0.85; P < 0.01), and there was no significant evidence that this association was nonlinear (P = 0.73 for nonlinearity test).
Other Beverages and Risk of Kidney Stones
After excluding multiple publications, 3 studies30,36,38 reported on the association between juice intake and risk of kidney stones, 4 studies29,30,36,38 reported on the association between soda intake and risk of kidney stones, and 5 studies30,31,36,38,39 reported on the association between milk consumption and kidney stone risk. Limited studies reported data that could be used for dose–response analyses. The overall meta-analysis showed that, compared to those with no juice consumption, those with 1 to 2 cups per day of juice intake had a RR of kidney stones of 1.02 (95% CI: 0.95, 1.10; P = 0.64; I2 = 0.0%); compared to those with no soda consumption, those with 1 to 2 cups per day of soda intake had a RR of kidney stones of 1.03 (95% CI: 0.90, 1.17; P = 0.65; I2 = 42.6%). Additionally, compared to those with no milk consumption, those who consumed 1 to 2 cups of milk per day had a kidney stone RR of 0.96 (95% CI: 0.88, 1.03; P = 0.21; I2 = 0.0%) (see Figure 6).
Subgroup Analysis and Sensitivity Analysis
Subgroup analyses were conducted on country, study design, and other subtypes (if reported, such as sex). Apart from coffee and alcohol, no substantial changes of the results were found between subgroups (Table 2).
For coffee intake, the kidney stone RR associated with 1 to 2 servings of coffee per day was not significant in the subgroup of case–control studies (RR = 0.85, 95% CI: 0.64, 1.13; P = 0.26; I2 = 41.7%). A subgroup analysis showed that alcohol intake was not associated with a lower risk of kidney stones (RR = 0.76, 95% CI: 0.46, 1.25; P = 0.28; I2 = 86.6%) in case–control studies. Variation among other subgroups could not be assessed reliably due to small numbers.
As to heterogeneity of results, in most cases, the case–control studies showed a greater heterogeneity than cohort studies. Additionally, studies conducted in the United States showed mild heterogeneity, while considerably greater degrees of heterogeneity were observed in studies conducted in other countries (Finland, British).
Sensitivity analyses were conducted by omitting 1 study at a time to see whether the omission of the study influenced the overall results. We found that, for alcohol intake (about 12 g), 2 studies27,39 substantially influenced the results, as omitting either study led the results to become statistically significant (RRomit27 = 0.78, 95% CI: 0.61, 0.99; RRomit39 = 0.77, 95% CI: 0.61, 0.97). For milk intake, when omitting study,30 the results reached to statistical significant (RR = 0.90, 95% CI: 0.82, 0.98). Other fluids showed robust results.
The meta-analysis results for water, tea, and alcohol intake were examined for publication bias (there were not enough studies to conduct publication bias analyses for other beverages). Egger's regression test of publication bias did not show strong evidence of publication bias (P for water = 0.92, P for tea = 0.55, P for alcohol = 0.76).
This is the first meta-analysis to have investigated the association of different types of beverages with risk of kidney stones. The meta-analysis confirmed that water intake was associated with a reduced risk of kidney stones. It also found that coffee, tea, and alcohol intake may reduce the risk of kidney stones. In contrast, juice, soda, and milk intake were not associated with kidney stone risk. Further subgroup analyses and sensitivity analyses showed unstable results for coffee and alcohol.
By increasing urine volume, increased water intake can dilute urine concentration, reduce CaOx super saturation, decrease urine acid, and remove salt.6,41 The European Association of Urology guidelines42 suggest that daily water intake should achieve at least 2.5 L of urine volume in order to prevent kidney stones. The present meta-analysis found no obvious threshold at which water intake began to be associated with reduced kidney stone risk. Instead, any increase in water intake, even at low levels of intake, was associated with reduced kidney stone risk. Thus, an average daily water intake should be recommended. The results of the present meta-analysis are partly consistent with a previous meta-analysis,10 which found that increased fluid intake (>2000 mL/day) was associated with a 61% reduction in the risk of kidney stones. Another conference abstract43 comparing the highest versus lowest level of total fluid intake, observed a 60–80% deceased risk of kidney stone in the highest level group. In our meta-analysis, greater than 2000 mL of water intake per day reduced the risk of first kidney stone occurrence risk by at least 8% compared to 1500 mL daily intake, and the highest (3100 mL) category showed a 26% reduction of kidney stone risk compared to the reference category (1500 mL). Compared to the earlier meta-analysis, our meta-analysis quantitatively evaluated the effects of different doses of water intake and thus provides more refined information.
Caffeine, which is present in both in coffee and tea, is a potential risk factor for kidney stones because it may increase the urinary calcium/creatinine ratio.44 In our study, coffee and tea intake were associated with a reduced risk of kidney stones when modeled as a continuous variable but not as a dichotomous variable. This may suggest a dose-dependent relationship between coffee (and tea) intake in prevention of stones. It is possible that some beneficial substances in coffee and tea (such as calcium)34 offset the influence of caffeine. But this result may be influenced by the inconsistency between different study designs. Further studies, especially based on cohort design, were needed.
Tea consumption appeared to show a borderline nonlinear relationship with kidney stone risk, with a reduction in risk seen mostly at intake levels above 250 mL/day. Animal experiments support this result.45,46 In rats, green tea consumption significantly decreased urinary oxalate excretion and calcium oxalate deposit formation, possibly by the antioxidative action of epigallocatechin gallate and the activity of superoxide dismutase.45,46 However, it is difficult to explain why a reduction in kidney stone risk would only occur above a certain threshold of tea consumption, though increased consumption of water might partially explain such a threshold effect.
Our meta-analysis on alcohol consumption showed inconsistent results. Although 12 g of alcohol intake showed no prevention effect on stone formation, the dose–response meta-analysis indicates alcohol intake was associated with a reduced risk of kidney stones. Our subgroup analysis also showed inconsistent results by study design and country, indicating the potential benefit effect on stone prevention. There are limited studies focusing on the mechanism by which alcohol intake could affect kidney stone risk. One possible mechanism may be the diuretic action of alcohol.47 This hypothesis may also partly explain why tea and coffee are associated with a reduced risk of kidney stones. But our results for alcohol were not particularly stable, and should therefore be interpreted with caution.
For juice intake, the overall meta-analysis showed no association between juice intake and risk of kidney stones. But the limited number of studies may results in bias. Moreover, the present study did not have sufficient data on the relation of lemon juice, cranberry juice, or pomegranate juice to kidney stone risk, though previous studies have reported that these juices are associated with a reduction in kidney stone risk.48–51 Further studies are needed.
Regarding soft drinks, the meta-analysis of Fink et al10 showed that decreased soft drink intake lowered the risk of kidney stones in patients with a high baseline consumption of soft drinks. In our meta-analysis, 110 to 240 mL of soda intake per day was not associated with stone risk. But the present study had no more data on other doses intake and the risk of stones.
In our meta-analysis, milk intake (about 1–2 servings a day) was not associated with kidney stone risk. Subgroup analyses also failed to find associations of whole or skim milk with kidney stone risk. The effect of higher doses of milk intake is still not known. But in the large cohort study of Goldfarb et al,39 intake of 5 or more cups of milk intake a day was not associated with stone risk.
We should note that confounding factors may have influenced our results.52 The most important confounder is water intake, for each type of beverage contains large amounts of water. It is difficult to control for the confounding influence of water, either by study design or by statistical adjustment. Therefore, the effects of coffee, tea, and alcohol may be overestimated while the effects of juice, soda, and milk may be underestimated. That is, coffee, tea, and alcohol may actually be less protective against kidney stone risk than our results suggest. Conversely, juice, soda, and milk intake may increase the risk of kidney stone more than is suggested by our results, since water may offset part of the risk associated with those beverages. Other variables, such as genetic factors,53 hardness of drinking water,54 concentration of beverages, body mass index,35 and geographical environment55 (such as desert) may also potentially confound the association between fluid intake and kidney stone risk. However, our sensitivity analyses showed that our results were robust, which suggests that the influence of confounders in our study was mild.
Strength and Limitations
The present study's comprehensive literature search, and strict study design, lends credibility to the study's results. Linear and nonlinear dose–response meta-analysis quantitatively evaluated the association of different levels of beverages intake on kidney stone risk, providing a more refined analysis than some prior studies. Additionally, subgroup and sensitivity analyses suggested that our study's results were robust in most cases, which strengthens the conclusions of our study.
This present study had some limitations. One limitation was that our evaluation and transformation of the raw data was fairly crude. A second limitation was that there were limited numbers of cohort studies focusing on the association between fluid intake and the risk of kidney stones. This small number of cohort studies is potentially problematic, since some research indicates that random errors induced by a small numbers of trials may cause bias in the results of meta-analyses.56,57 A third limitation was that different categories of fluid intake among studies made it difficult to pool results across studies. Indeed, some studies only reported the effect of any versus no fluid intake, or high versus no intake, while others reported 110 mL versus no intake of fluids. Although dose–response meta-analysis was used to overcome this problem, for soda and milk, there were limited studies reporting relevant data that could be used in a dose–response analysis. Furthermore, differences in how studies categorized fluid intake may have contributed to some of the heterogeneity we observed in our results, especially for juice intake. A fourth limitation was that, in our meta-analysis, most of the studies were conducted in the United States and China, and may not be generalizable to other countries. Fifth, we did not examine interactions among subgroups because the subgroup sample sizes were too small for such analyses to produce statistically reliable results.
Increased water are associated with a reduced risk of developing kidney stones; increased intake of coffee, tea, and alcohol showed potential benefits on stones prevention, but needs to be confirmed further. Soda and milk intake appeared to be unrelated to stone risk. Current evidence is insufficient for definitively determining the relationship between juice intake and risk of kidney stones.
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