Mechanisms of malnutrition in uremia.
The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.
Guarnieri
G
G
Istituto di Clinica Medica, University of Trieste, Italy. GIANFRANG@CLMED.UNIV.TRIESTE.IT
Toigo
G
G
Fiotti
N
N
Ciocchi
B
B
Situlin
R
R
Giansante
C
C
Vasile
A
A
Carraro
M
M
Faccini
L
L
Biolo
G
G
D000328:Adult; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011502:Protein-Energy Malnutrition / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014511:Uremia / Q000378:metabolism / Q000503:physiopathology*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine