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Int J Biol Sci. 2017 Jul 18;13(8):961-975. doi: 10.7150/ijbs.20074. eCollection 2017.

Vasopressin Mediates the Renal Damage Induced by Limited Fructose Rehydration in Recurrently Dehydrated Rats.

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Laboratory of Renal Physiopathology. INC Ignacio Chávez. Mexico City. Mexico.
Dept. of Nephrology. INC Ignacio Chávez. Mexico City. Mexico.
Dept. of Cardiovascular Biomedicine. INC Ignacio Chávez. Mexico City. Mexico.
Dept. of Biology. Faculty of Chemistry, UNAM. Mexico City. Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, IPN Mexico City. Mexico.
Dept. of Pathology. INC Ignacio Chávez. Mexico City. Mexico.
Div. of Renal Diseases, University of Colorado, Aurora CO, USA.


Recurrent dehydration and heat stress cause chronic kidney damage in experimental animals. The injury is exacerbated by rehydration with fructose-containing beverages. Fructose may amplify dehydration-induced injury by directly stimulating vasopressin release and also by acting as a substrate for the aldose reductase-fructokinase pathway, as both of these systems are active during dehydration. The role of vasopressin in heat stress associated injury has not to date been explored. Here we show that the amplification of renal damage mediated by fructose in thermal dehydration is mediated by vasopressin. Fructose rehydration markedly enhanced vasopressin (copeptin) levels and activation of the aldose reductase-fructokinase pathway in the kidney. Moreover, the amplification of the renal functional changes (decreased creatinine clearance and tubular injury with systemic inflammation, renal oxidative stress, and mitochondrial dysfunction) were prevented by the blockade of V1a and V2 vasopressin receptors with conivaptan. On the other hand, there are also other operative mechanisms when water is used as rehydration fluid that produce milder renal damage that is not fully corrected by vasopressin blockade. Therefore, we clearly showed evidence of the cross-talk between fructose, even at small doses, and vasopressin that interact to amplify the renal damage induced by dehydration. These data may be relevant for heat stress nephropathy as well as for other renal pathologies due to the current generalized consumption of fructose and deficient hydration habits.


Vasopressin; chronic kidney disease

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing Interests: RJJ and CARJ have patent applications related to blocking fructose metabolism as a means to prevent acute and chronic kidney disease. RJJ also has funding from Amway and is on the Scientific Board of Amway. RJJ also has grants from Questcor, the NIH, and the State of Colorado and is a member of Colorado Research Partners. The other authors have no conflict of interest to declare.

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