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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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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. |
format | Online Article Text |
id | pubmed-4120672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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