Fructokinase activity mediates dehydration-induced renal injury.

Kidney International
Carlos A Roncal JimenezRichard J Johnson

Abstract

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the ...Continue Reading

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Aug 26, 2014·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Ricardo Correa-RotterRichard J Johnson
Jan 15, 2014·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Ricardo Correa-RotterRichard J Johnson
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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
biopsy

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