The prevalence of chronic kidney disease more than doubled from 1988 to 2001, affecting more than 20 million adults in the United States.1,2 Since the incidence of kidney disease and associated health care costs are expected to continue to rise,3,4 identifying modifiable risk factors is a public health priority.5,6
Well-documented risk factors for kidney disease include diabetes, hypertension, and family history.7,8 Kidney stones may also increase risk,9 and soft-drink consumption has been associated with diabetes,10 hypertension,11 and kidney stones.12–14 Cola beverages, which are acidified with phosphoric acid, have been associated with urinary changes known to promote kidney stones.13,15,16 Current recommendations for patients with kidney disease or kidney stones include avoiding cola beverages,17,18 but there is limited evidence to support this recommendation.
In this paper, we examine the association between carbonated beverage intake and chronic kidney disease.
METHODS
We used data from a case-control study of North Carolina patients with chronic kidney disease and community controls.19 Trained personnel identified potential cases by reviewing medical charts from 4 North Carolina hospitals. Cases were included if they were newly diagnosed with kidney disease between September 1980 and August 1982 and had a sustained elevation in serum creatinine (2 or more measurements ≥130 μmol/L). Patients younger than 30 years or who resided outside of North Carolina were excluded. Patients with preexisting kidney disease, polycystic kidney disease, systemic lupus erythematosus, multiple myeloma, amyloidosis, or hereditary nephritis were also excluded.
Of 709 patients found eligible, 607 (86%) could be contacted and 554 (78%) agreed to participate. We excluded individuals who were missing data for carbonated beverages (n = 25) or potential confounders (n = 64), leaving 465 cases for analysis. Patients were classified into kidney disease subtypes using available clinical and laboratory information.
Community controls were selected using random digit dialing for those younger than 65 years of age, and Medicare recipient listing for those 65 years of age or older. Controls were frequency-matched to cases by age (within 5 years), sex, race, and proximity to a study hospital. Of 717 potential controls, 608 (85%) could be contacted and 520 (73%) agreed to participate. We excluded individuals with history of kidney disease (n = 4), and those with missing data on beverage consumption (n = 18) or on potential confounders (n = 31), leaving 467 for analysis.
Information was collected through telephone interviews. Subjects or proxy respondents were asked about beverage consumption over their adult life. The question was “Please tell me about your drinking habits before 1980. Since you were 18-years-old did you ever drink (list of individual beverages) and, if so, how many times per day, week, month, or year did you usually drink the beverage?” Questions were asked separately about regular cola, artificially sweetened cola, noncola caffeinated beverages, and noncola artificially sweetened beverages. Average intake of water, coffee, and tea was also recorded. At the time of the interviews (1982–1983) noncaffeinated teas and colas were uncommon, and thus tea and cola were assumed to contain caffeine. Total caffeine from noncola sources was calculated by assigning an average caffeine content of 80 mg per cup of coffee, 40 mg per cup of tea, and 40 mg per glass of other caffeinated beverages.
We used unconditional logistic regression to estimate the association between carbonated beverages and chronic kidney disease. We identified potential confounders based on their known association with beverage consumption and kidney disease. We retained in the final model covariates that resulted in at least a 10% change in the coefficient. We examined the following variables as potential confounders: body mass index (BMI), education, income, smoking, analgesic use, alcohol use, caffeine from noncola sources, fluid intake from noncola sources, history of diabetes, hypertension, kidney stones, and proxy respondent status. We also explored effect modification by history of diabetes, hypertension, or kidney stones through stratified models and by modeling interaction terms. Additionally, we performed separate analyses for specific diagnostic subgroups.
RESULTS
Compared with controls, cases more frequently reported a lower income and educational level, had a higher mean BMI, and reported more frequent use of analgesic medications, as well as a history of diabetes, hypertension, and kidney stones (Table 1). Proxy respondents were more frequent for cases than controls (54% vs. 10%). Consumption of cola was higher among cases, as was fluid intake from noncola sources. Caffeine intake from noncola sources was similar between cases and controls.
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TABLE 1: Selected Characteristics of Patients With Chronic Kidney Disease and Community Controls in the North Carolina Health Study, 1980–1982 (n = 932)
Consumption of 2 or more glasses of cola per day was associated with a 2-fold risk of kidney disease compared with the reference category, after adjusting for age, race, sex, proximity to study hospital, BMI, income, proxy respondent status, education, analgesic use, and diabetes (Table 2). Estimates for regular colas or artificially sweetened colas were similar. Increasing quantities of noncola carbonated beverages, caffeine from noncola sources, and intake of fluids from sources other than cola were not associated with kidney disease risk. Results were similar after excluding proxy respondents (Table 2) and for those without diabetes, hypertension, or history of kidney stones (Table 3). We assessed robustness of the finding by assigning high cola consumption to controls with missing data and then by assigning no cola consumption to cases with missing data. Neither assumption materially changed the results (data not shown). Table 4 presents the adjusted odds ratios for specific diagnostic subgroups of chronic kidney disease in relation to all colas combined.
TABLE 2: Risk of Chronic Kidney Disease Associated With Carbonated Beverage Consumption, Caffeine Intake, and Noncola Fluid Intake Among all Subjects and Among Self-Respondents
TABLE 3: Risk of Chronic Kidney Disease Associated With Increasing Levels of Carbonated Cola Consumption, Stratified by Self-reported Diabetes, Hypertension, and Kidney Stones
TABLE 4: Risk of Chronic Kidney Disease Associated With Increasing Levels of Cola Consumption Overall and by Subtype of Chronic Kidney Disease
DISCUSSION
Our analysis suggests that consumption of 2 or more cola beverages per day was associated with an increased risk of chronic kidney disease. We saw no increase in risk associated with consumption of noncola carbonated beverages, or with noncola caffeinated beverages.
Although we know of no previous study that assesses a link between cola beverages and kidney disease, there is evidence supporting the plausibility of our findings. One difference between cola and noncola carbonated beverages is that, while noncola beverages have been predominantly acidified using citric acid, cola beverages are generally acidified using phosphoric acid. Phosphorus may have an effect on the risk of kidney disease. Case reports have linked sodium phosphate bowel cleansing preparations to acute and sometimes irreversible renal failure,20,21 characterized by calcium phosphate deposits in the distal tubules and collection ducts or nephrocalcinosis.22–24 Although the level of phosphorus from colas is far lower than that from bowel preparations, long-term cola intake may lead to kidney damage, especially in the presence of underlying renal dysfunction.
Laboratory studies have shown that high phosphorus diets can cause nephrocalcinosis in rats.25,26 Diets high in phosphate may increase plasma phosphorus levels, with phosphate in colas perhaps being more bioavailable.27,28
In a randomized trial among men with kidney stones, recurrence of kidney stones was higher among those who continued to drink soft drinks containing phosphoric acid, compared with those who drank beverages acidified by citric acid.13 Cola consumption can result in physiologic changes in urine composition that are conducive to oxalate kidney stone formation.15,16,29,30 We saw no association with cola among individuals with history of kidney stones, although the sample size for this subanalysis was small.
The odds ratios for a cola association were higher among those with a history of diabetes, although the test for interaction was not statistically significant. A recent study has shown a positive association between cola beverages and incidence of hypertension.11 In our analysis we saw no evidence of effect modification by hypertension, nor did hypertension confound our results.
We cannot rule out the possibility that the observed effect may have been due to caffeine, but we did not see an increasing risk with increasing consumption of caffeine from noncola sources.
This study had several limitations. We were not able to examine dietary differences between cases and controls or between cola and noncola drinkers. Cola drinkers may also differ from noncola drinkers in other ways that could lead to residual confounding. Among controls, cola drinkers were younger, less likely to have a history of diabetes, and more likely to have a history of kidney stones compared with noncola drinkers. We controlled for age and diabetes, and history of kidney stones was not a confounder.
The high proportion of proxy respondents among cases is a further limitation. However, the estimated effect of cola was stronger after excluding proxy respondents, suggesting that their inclusion attenuated the estimated risk.
Beverage consumption was self-reported and thus subject to potential bias. However, since a link between carbonated beverage intake and risk of kidney disease was unknown at the time of the study, it is unlikely that cases would have differentially reported their beverage consumption. In this analysis, only colas were consistently associated with chronic kidney disease, which makes reporting bias an unlikely explanation for our findings.
Participants reported average beverage intake over their adult life. While these reports may reflect more recent consumption, there is no reason to believe that those who currently drank colas had not done so in the past. Colas have been available since the late 1800s and were first popularized in the southern United States.
Cola consumption is common and chronic kidney disease is a substantial public health burden. Our preliminary result of an association between cola consumption and risk of chronic kidney disease deserves to be explored in more detailed studies.
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