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RESEARCH PRODUCT

Aestivation Motifs Explain Hypertension and Muscle Catabolism in Experimental Chronic Renal Failure

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Chronic renal failure leads to muscle mass loss and hypertension, which according to textbook teaching occur secondary to an inability of the kidneys to excrete solutes and water. We found instead that rats with experimental chronic renal failure constantly lost body water, because their kidneys could not sufficiently concentrate the urine. Physiological adaptation to body water loss, termed aestivation, is an evolutionary conserved survival strategy that relies on complex physiologic-metabolic adjustment across multiple organs to prevent otherwise lethal dehydration. We show that rats with chronic renal failure utilize these ancient water conservation motifs to successfully stabilize their body water. Metabolic aestivation responses to chronic renal failure require nitrogen-rich organic osmolyte production. Continuous endogenous energy and nitrogen supply from skeletal muscle in support of this metabolic requirement explains “renal” muscle mass loss. Accompanying circulatory aestivation responses are designed to limit skin water loss. This process requires vasoconstriction, which explains “renal” hypertension.