Merck

Fructokinase activity mediates dehydration-induced renal injury.

Kidney international (2013-12-18)
Carlos A Roncal Jimenez, Takuji Ishimoto, Miguel A Lanaspa, Christopher J Rivard, Takahiko Nakagawa, A Ahsan Ejaz, Christina Cicerchi, Shinichiro Inaba, MyPhuong Le, Makoto Miyazaki, Jason Glaser, Ricardo Correa-Rotter, Marvin A González, Aurora Aragón, Catharina Wesseling, Laura G Sánchez-Lozada, Richard 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 dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-(−)-Fructose, BioUltra, ≥99.0% (HPLC)
Millipore
D-(−)-Fructose, ≥99.0% (HPLC), suitable for microbiology
Sigma-Aldrich
D-(−)-Fructose, tested according to Ph. Eur.
Supelco
D-(−)-Fructose, analytical standard, analytical standard for fructose assay kit, for use with enzymatic assay kit FA20
Sigma-Aldrich
D-(−)-Fructose, BioXtra
Sigma-Aldrich
D-(−)-Fructose, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
D-(−)-Fructose, ≥99%
Sigma-Aldrich
D-(−)-Fructose, meets USP testing specifications
Supelco
Fructose, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-(−)-Fructose, SAJ special grade, ≥98.0%
Sigma-Aldrich
D-(−)-Fructose, LR
USP
Fructose, United States Pharmacopeia (USP) Reference Standard
Fructose, European Pharmacopoeia (EP) Reference Standard