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Fructokinase activity mediates dehydration-induced renal injury

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 mi...

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Autores principales: Roncal Jimenez, Carlos A, Ishimoto, Takuji, Lanaspa, Miguel A, Rivard, Christopher J, Nakagawa, Takahiko, Ejaz, A. Ahsan, Cicerchi, Christina, Inaba, Shinichiro, Le, MyPhuong, Miyazaki, Makoto, Glaser, Jason, Correa-Rotter, Ricardo, González, Marvin A, Aragón, Aurora, Wesseling, Catharina, Sánchez-Lozada, Laura G, Johnson, Richard J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120672/
https://www.ncbi.nlm.nih.gov/pubmed/24336030
http://dx.doi.org/10.1038/ki.2013.492
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author Roncal Jimenez, Carlos A
Ishimoto, Takuji
Lanaspa, Miguel A
Rivard, Christopher J
Nakagawa, Takahiko
Ejaz, A. Ahsan
Cicerchi, Christina
Inaba, Shinichiro
Le, MyPhuong
Miyazaki, Makoto
Glaser, Jason
Correa-Rotter, Ricardo
González, Marvin A
Aragón, Aurora
Wesseling, Catharina
Sánchez-Lozada, Laura G
Johnson, Richard J
author_facet Roncal Jimenez, Carlos A
Ishimoto, Takuji
Lanaspa, Miguel A
Rivard, Christopher J
Nakagawa, Takahiko
Ejaz, A. Ahsan
Cicerchi, Christina
Inaba, Shinichiro
Le, MyPhuong
Miyazaki, Makoto
Glaser, Jason
Correa-Rotter, Ricardo
González, Marvin A
Aragón, Aurora
Wesseling, Catharina
Sánchez-Lozada, Laura G
Johnson, Richard J
author_sort Roncal Jimenez, Carlos A
collection PubMed
description 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.
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spelling pubmed-41206722014-08-15 Fructokinase activity mediates dehydration-induced renal injury Roncal Jimenez, Carlos A Ishimoto, Takuji Lanaspa, Miguel A Rivard, Christopher J Nakagawa, Takahiko Ejaz, A. Ahsan Cicerchi, Christina Inaba, Shinichiro Le, MyPhuong Miyazaki, Makoto Glaser, Jason Correa-Rotter, Ricardo González, Marvin A Aragón, Aurora Wesseling, Catharina Sánchez-Lozada, Laura G Johnson, Richard J Kidney Int Basic Research 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. Nature Publishing Group 2014-08 2013-12-11 /pmc/articles/PMC4120672/ /pubmed/24336030 http://dx.doi.org/10.1038/ki.2013.492 Text en Copyright © 2014 International Society of Nephrology http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Basic Research
Roncal Jimenez, Carlos A
Ishimoto, Takuji
Lanaspa, Miguel A
Rivard, Christopher J
Nakagawa, Takahiko
Ejaz, A. Ahsan
Cicerchi, Christina
Inaba, Shinichiro
Le, MyPhuong
Miyazaki, Makoto
Glaser, Jason
Correa-Rotter, Ricardo
González, Marvin A
Aragón, Aurora
Wesseling, Catharina
Sánchez-Lozada, Laura G
Johnson, Richard J
Fructokinase activity mediates dehydration-induced renal injury
title Fructokinase activity mediates dehydration-induced renal injury
title_full Fructokinase activity mediates dehydration-induced renal injury
title_fullStr Fructokinase activity mediates dehydration-induced renal injury
title_full_unstemmed Fructokinase activity mediates dehydration-induced renal injury
title_short Fructokinase activity mediates dehydration-induced renal injury
title_sort fructokinase activity mediates dehydration-induced renal injury
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120672/
https://www.ncbi.nlm.nih.gov/pubmed/24336030
http://dx.doi.org/10.1038/ki.2013.492
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