Brain activation in uremic anorexia.
This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.
Aguilera
Abelardo
A
Servicio de Nefrologia, Hospitales Universitarios de la Princesa y la Paz, Madrid, Spain. aguileraa@terra.es
Sánchez-Tomero
José Antonio
JA
Selgas
Rafael
R
D000596:Amino Acids / Q000378:metabolism; D000855:Anorexia / Q000276:immunology*; D001069:Appetite Regulation / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D020738:Leptin / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014511:Uremia / Q000150:complications / Q000503:physiopathology*
D000596:Amino Acids; D016207:Cytokines; D020738:Leptin; D009569:Nitric Oxide; D012701:Serotonin