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The perils of rehydrating with soft drinks following heat and exercise

2019; American Physiological Society; Volume: 316; Issue: 3 Linguagem: Inglês

10.1152/ajpregu.00007.2019

1522-1490

Laura Gabriela Sánchez‐Lozada, Carlos A. Roncal-Jiménez, Fernando E. García‐Arroyo, Thomas Jensen, Miguel A. Lanaspa, Richard J. Johnson,

Coffee research and impacts

Editorial FocusThe perils of rehydrating with soft drinks following heat and exerciseLaura G. Sánchez-Lozada, Carlos A. Roncal-Jimenez, Fernando E. García-Arroyo, Thomas Jensen, Miguel A. Lanaspa, and Richard J. JohnsonLaura G. Sánchez-LozadaDepartment of Nephrology, Instituto Nacional de Cardiología-Ignacio Chavez. Mexico City. Mexico, Carlos A. Roncal-JimenezRenal Diseases and Hypertension. University of Colorado, Aurora, Colorado, Fernando E. García-ArroyoDepartment of Nephrology, Instituto Nacional de Cardiología-Ignacio Chavez. Mexico City. Mexico, Thomas JensenRenal Diseases and Hypertension. University of Colorado, Aurora, Colorado, Miguel A. LanaspaRenal Diseases and Hypertension. University of Colorado, Aurora, Colorado, and Richard J. JohnsonRenal Diseases and Hypertension. University of Colorado, Aurora, ColoradoPublished Online:21 Feb 2019https://doi.org/10.1152/ajpregu.00007.2019This is the final version - click for previous versionMoreSectionsPDF (55 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Intake of sugary beverages, and especially soft drinks, increases the risk of obesity and diabetes. But they are now emerging as a major risk factor for kidney disease. Sugary beverages contain ~11% sugar content, either as sucrose (a disaccharide of fructose and glucose) or as high-fructose corn syrup (HFCS), the latter a mixture of fructose and glucose monosaccharides in a 55-to-45 relative ratio. Intake of soft drinks increased markedly over the last century but has been steadily decreasing in the United States since 2005. However, this has been partially compensated by increased intake of other sugary beverages, including energy drinks, sports drinks, and juices. Today ~5 to 7% of the overall energy intake comes from sugary beverages.Epidemiological studies have linked soft drink intake with kidney disease. The first major association noted was with kidney stones (16). The fructose present in soft drinks generates uric acid during its metabolism, resulting in acute uricosuria with a fall in urine pH (10). Urate crystalluria may result, which can result in urate stones as well as acting as a nidus for calcium-based kidney stones. Soft drinks are also known to result in urinary concentration and volume contraction, which is thought to be due to slowed gastric emptying and a loss of fluid into the gut (12). The urinary concentration that results may result in an increased risk of kidney stones. Indeed, it has been reported that reducing soft drink intake can lead to a reduction in the rate of recurrence of kidney stones (15).Soft drink intake has also been reported to increase the risk for chronic kidney disease (CKD) in some but not all studies (3). However, a recent meta-analysis provided evidence that, overall, it is a risk factor for CKD (3). Most evidence suggests that the risk is greater for sugary soft drinks as opposed to diet soft drinks. Several mechanisms may account for this association. First, while low concentrations of fructose are metabolized by the gut, higher concentrations, such as present in soft drinks, reach the liver and kidney (9). Fructose filtered by the glomeruli is taken up by the proximal tubule where it is metabolized rapidly by the enzyme fructokinase, resulting in intracellular phosphate depletion, uric acid generation, the development of oxidative stress, and the release of inflammatory chemotactic factors (4). This may result in acute proximal tubular injury and over time may lead to interstitial fibrosis and inflammasome-associated intrarenal inflammation, as demonstrated in animal models (6, 11). Fructose metabolism can also result in uricosuria in the absence of stones that may lead to tubular injury. Indeed, in a study in diabetics, the abolition of glucose-induced urate crystalluria with oral bicarbonate resulted in a decrease in urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL, a biomarker of kidney disease) (1). In addition, soft drinks may contain other substances that may increase the risk of kidney disease. Thus, colas contain high concentrations of phosphate, which may chelate with calcium in vivo and increase the risk for acute kidney injury, especially in subjects with underlying CKD (5). Some evidence indicates increased risk of CKD in subjects drinking phosphate-rich colas as opposed to other soft drinks (14). Thus both fructose-dependent and fructose-independent mechanisms for kidney disease have been proposed.Recently there has been interest in the role of fructose in mediating kidney injury associated with heat stress. In this regard, epidemics of CKD have been recognized in several regions of the world in which a major risk factor appears to be heat stress. One of the primary areas is in Central America where epidemics of CKD have been reported among sugarcane workers. The results of several studies suggest that these individuals are developing repeated acute kidney injury in association with heat stress and dehydration, and there is limited evidence that this may increase the risk for CKD over time (8, 17). Experimental studies suggests that the renal damage may be mediated by recurrent dehydration that leads to activation of the aldose reductase (polyol) pathway in the kidney, resulting in endogenous fructose production (13), as well as by chronic effects of vasopressin (7). The local metabolism of fructose, coupled with the effects of vasopressin, are thought to mediate kidney injury that over time may increase the risk for CKD.In this setting, the intake of soft drinks might exacerbate kidney injury several ways. First, it could provide an exogenous source of fructose that could accelerate kidney disease. In addition, recent reports indicate that fructose also stimulates vasopressin release that could potentiate vasopressin-mediated renal injury (7, 18). Indeed, in an experimental study, rehydration with fructose-containing solutions in heat-stressed rats resulted in higher serum levels of vasopressin (copeptin), higher intrarenal fructokinase expression, greater intrarenal oxidative stress, increased tubular injury, and worse renal function compared with water-hydrated rats (6). However, until now there has been little or no evidence that rehydration with soft drinks has potentially deliterious effects in humans.In this issue, Chapman et al. (2) describe an evaluation of the effects of soft drink rehydration in heat-stressed humans. Specifically, young healthy individuals were subjected to 4 h of heat (35°C, 61% humidity) during which they exercised for 4 h (split up as 45 min exercise followed by 15 min rest) at a heart rate of 55% of maximum. On one occasion they were hydrated with Mountain Dew (2 liters during exercise and 1 liter immediately after) and on the other occasion they received water. The primary finding was that hydration with soft drinks resulted in a significant decrease in plasma volume, with a mean rise in serum creatinine of 0.3 mg/dl, and a slight but significant increase in overnight urine NGAL (a biomarker of renal injury) with a decrease in urine flow. In contrast, serum creatinine only increased 0.05 mg/dl with water rehydration and plasma volume was minimally reduced. Therefore, these studies represent the first evidence in humans that rehydration with sweetened beverages after heat stress can induce acute kidney injury.There are several important caveats to the current study. First, the decrease in renal function likely is mediated in part by extracellular volume contraction, possibly related to fluid sequestration in the gut, and hence, may not involve structural injury to the kidney. Second, it would have been ideal to include a control group receiving diet Mountain Dew that had identical components other than the added sugar. Nevertheless, the importance of the finding is that the rise in serum creatinine was quite marked (0.3 mg/dl) which would normally be considered to reflect acute kidney injury. These findings emphasize the importance of performing more studies to better understand how soft drinks may contribute to acute kidney injury and CKD.Sugary beverage intake, especially of soft drinks, is emerging as an important risk factor for kidney and metabolic disease. Studies such as that reported in the paper by Chapman et al. in this issue of the journal add to the body of evidence emphasizing the previously unrecognized importance of sugar intake as a risk factor for kidney disease. We suggest that, when a medical history is obtained, one should ask about intake of sugar, and especially sugary beverages, similar to what one does for smoking and alcohol intake. Reducing soft drink intake could provide major benefits, not only in reducing the risk for metabolic syndrome and diabetes, but also reducing the risk of kidney stones and acute and chronic kidney disease.GRANTSThis paper was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK109408.DISCLOSURESL. G. Sanchez-Lozada, C. A. Roncal-Jimenez, M. A. Lanaspa, and R. J. Johnson have equity in a startup company (Colorado Research Partners LLC) that is developing inhibitors of fructose metabolism. R. J. Johnson also has received honoraria from Danone Research Foundation, Eli Lilly, Astra Zeneca and Horizon Pharmaceuticals.AUTHOR CONTRIBUTIONSL.G.S.-L., C.A.R.-J., F.E.G.-A., T.J., and M.A.L. edited and revised manuscript; C.A.R.-J., F.E.G.-A., and M.A.L. approved final version of manuscript; R.J.J. drafted manuscript.REFERENCES1. 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Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: L. G. Sanchez-Lozada, Laboratory of Renal Physiopathology, Dept. of Nephrology. INC Ignacio Chávez, Juan Badiano 1, 14080 Tlalpan, Mexico City, Mexico (e-mail: [email protected]com). 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