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Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase

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Technical Report,30 Sep 2014,29 Sep 2015

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University of Colorado, Denver Aurora United States

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Our studies evaluate how recurrent dehydration can cause chronic kidney disease, an important question for the military and public. We hypothesize, based on preliminary data, that dehydration associated renal injury results from hyperosmolarity induced activation of renal aldose reductase-fructokinase. We have made good progress and are on target for completing all studies. Aim 1 test the role of selective renal knockout of fructokinase in dehydration induced kidney disease, and we have now generated the floxed fructokinase mouse that is critical for conducting these studies. Aim 2 investigates the role of vasopressin receptors and uric acid, and we have completed studies of the Vasopressin 2 receptor and demonstrated vasopressin 2 receptors are responsible for some of dehydration induced kidney damage. Aim 3 tests the role of rehydration with fructose solutions with or without blocking of vasopressin receptors. These studies were delayed due to administrative issues but are ready to be completed and are still within our proposed milestones. In summary, we are documenting how recurrent dehydration causes chronic kidney disease, documenting a role for vasopressin and aldose reductase.

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