title: Metabolic consequences of uremia: extending the concept of adaptive responses to protein metabolism.
abstract: An early response to metabolic acidosis is an increase in the degradation of muscle protein to provide the nitrogen needed to increase glutamine production so the kidney can excrete acid. In patients with renal insufficiency, this process may represent an example of a trade-off adaptation to uremia. It requires a hormone (glucocorticoids) and the metabolic response is maladaptive because the inability of the damaged kidney to maintain acid-base balance results in loss of muscle protein. Studies of cultured cells and rats and humans with normal kidneys demonstrate that acidosis stimulates the degradation of both amino acids and protein, which would block the normal adaptive responses to a low-protein diet (ie, to reduce the degradation of essential amino acids and protein). Evidence from studies in rats and humans with chronic uremia show that acidosis is a major stimulus for catabolism. The mechanism includes stimulation of specific pathways for the degradation of protein and amino acids. Since other catabolic conditions (eg, starvation) appear to stimulate the same pathways, understanding the mechanism in acidosis could be applicable to other conditions. Thus, the loss of lean body mass in uremia appears to be a consequence of a normal metabolic response that persists until acidosis is corrected.
authors.affiliation: Renal Division, Emory University School of Medicine, Atlanta, GA.
authors.forename: W E
authors.initials: WE
authors.lastname: Mitch
authors.forename: S R
authors.initials: SR
authors.lastname: Price
authors.forename: R C
authors.initials: RC
authors.lastname: May
authors.forename: C
authors.initials: C
authors.lastname: Jurkovitz
authors.forename: B K
authors.initials: BK
authors.lastname: England
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D011506:Proteins