Malnutrition is an unusual cause of decreased muscle mass in chronic kidney disease.
Patients with chronic kidney disease (CKD), including those who are treated with hemodialysis, frequently develop hypoalbuminemia and a decrease in body weight. These abnormalities are usually attributed to malnutrition, but true malnutrition (ie, a disorder due to an abnormal diet) is rarely the mechanism causing decreased protein stores. Hypoalbuminemia is closely related to evidence of inflammation, and a decrease in muscle mass is caused by activation of muscle protein breakdown. In uremic rodents and patients, the initial step in the loss of muscle protein is activation of caspase-3, which cleaves the complex structure of muscle to provide substrates for the ubiquitin-proteasome pathway (UPP). The activity of caspase-3 can be detected by the presence of a characteristic 14-kDa actin fragment in the insoluble fraction of a muscle biopsy specimen. Abnormalities in cell signaling activate caspase-3 and the UPP; a key abnormality is decreased activity in the phosphatidylinositol-3-kinase/Akt pathway, leading to activation of caspase-3 and a specific E3 ubiquitin conjugating enzyme, atrogin-1/MAFbx. Inflammatory cytokines also represent a potential cell signaling abnormality that activates muscle protein breakdown, possibly because cytokines activate the E3 ubiquigin conjugating enzyme, MuRF1. An understanding of these pathways could help the clinician to identify therapeutic targets for preventing loss of muscle protein.
Mitch
William E
WE
Division of Nephrology, Baylor College of Medicine, Houston, Texas 77030, USA. mitch@bcm.edu
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002908:Chronic Disease; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology*; D044342:Malnutrition / Q000150:complications*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex