Written by Joyce Smith, BS. This study demonstrates in a mouse model that rehydration with fructose-containing beverages may lead to renal damage and hypertension.
Chronic kidney disease has reached epidemic proportions among Central American sugarcane workers, with over 20,000 deaths reported to date. Studies have implicated dehydration as the major risk factor 1,2. Working in hot environments can result in a loss of both salt and water, with usually a greater loss of water, leading to transient hyperosmolarity. In dehydration, the loss of water increases blood concentrations of sodium, glucose and other substances, which draws water out of the body’s other organs, including the brain. Hyperosmolarity, activates the aldose reductase-fructokinase pathway in which the pituitary release of vasopressin and the aldose reductase enzyme can lead to renal injury and chronic kidney disease 3. Aldose reductase, through the conversion of glucose to fructose, can damage renal tubules and incite inflammation 4,5. While dehydration activates this pathway, researchers speculate that the pathway might also be activated by fructose in sugar-sweetened drinks to exacerbate dehydration.
Knowledge of the ability of fructose, but not glucose or other sugars, to stimulate vasopressin release in humans 6 compelled the García-Arroyo team to investigate 7 whether fructose -containing beverages, when used for rehydration, could incite more kidney damage than recurrent dehydration alone over time. To that end they subjected three groups of Westar male rats to four weeks of daily heat-induced dehydration followed by two hours of rehydration during which one group rehydrated with a fructose-glucose (FG) drink (7.15% fructose, 3.85% glucose normally found in typical soft-drinks), a second group rehydrated with stevia-sweetened water and a third group rehydrated with regular water. These three groups were compared to a control group that was not subjected to heat dehydration.
After 4 weeks the rats were euthanized and kidneys prepared for histological examination and further analysis.
- Rehydration with water resulted in mild injury and oxidative stress in the kidneys, whereas rehydration with FG water resulted in 30% greater dehydration and worse renal injury in spite of larger total fluid intake. The renal cortex of these animals showed evidence of markers of oxidative stress and histological analysis revealed mild renal injury (renal tubular inflammation and damage). Rehydration with stevia water had opposite effects, maintaining hydration and preventing kidney damage.
- Blood pressure increased in the rats hydrating with FG and stevia waters compared to control rats; however, stevia water rehydration was associated with lower blood pressure than the control group.
- Dehydration was also associated with increased urinary sodium excretion (salt loss). This loss was further increased with FG water rehydration.
- Lastly, there was a significant increase in the expression of fructokinase, vasopressin receptors 1a and 2, and a further increase in the expression of aldose reductase. In contrast, the rats that rehydrated with stevia water did not manifest those changes.
Researchers could not explain the protective effect of stevia, whether the effect was due to the stevia group drinking significantly more water for rehydration compared to the regular water group or whether stevia itself was responsible for the effect. However, the study does clearly demonstrate that short-term rehydration with fructose-containing beverages in rats was associated with renal injury and hypertension caused by stimulation of the vasopressin and polyolfructokinase pathways and that these associations did not occur with ordinary water or stevia.
Source: García-Arroyo, Fernando E., Magdalena Cristóbal, Abraham S. Arellano-Buendía, Horacio Osorio, Edilia Tapia, Virgilia Soto, Magdalena Madero et al. “Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 311, no. 1 (2016): R57-R65.
© 2016 the American Physiological Society
Posted November 24, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Laws RL, Brooks DR, Amador JJ, et al. Changes in kidney function among Nicaraguan sugarcane workers. Int J Occup Environ Health. 2015;21(3):241-250.
- Peraza S, Wesseling C, Aragon A, et al. Decreased kidney function among agricultural workers in El Salvador. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2012;59(4):531-540.
- Bouby N, Bachmann S, Bichet D, Bankir L. Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. The American journal of physiology. 1990;258(4 Pt 2):F973-979.
- Cirillo P, Gersch MS, Mu W, et al. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. Journal of the American Society of Nephrology : JASN. 2009;20(3):545-553.
- Nakayama T, Kosugi T, Gersch M, et al. Dietary fructose causes tubulointerstitial injury in the normal rat kidney. American journal of physiology Renal physiology. 2010;298(3):F712-720.
- Wolf JP, Nguyen NU, Dumoulin G, Berthelay S. Influence of hypertonic monosaccharide infusions on the release of plasma arginine vasopressin in normal humans. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 1992;24(8):379-383.
- García-Arroyo FE, Cristóbal M, Arellano-Buendía AS, et al. Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury. American journal of physiology Regulatory, integrative and comparative physiology. 2016;311(1):R57-65.
