peptide-yy and Renal-Insufficiency

Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P < 0.001). Corresponding values for PYY(3-36) oscillated between 235 and 267 pg/mL in patients, versus 56 and 70 pg/mL in controls (P < 0.001). The association of high levels of PYY(3-36) and normal levels of acylated ghrelin (when compared with healthy controls) configurated a markedly pro-anorexigenic pattern in patients. Neither oral intake nor intraperitoneal glucose resulted in significant changes in plasma levels of PYY(1-36) or PYY(3-36) in subjects with renal failure, in contrast with the expected postprandial rise observed in healthy controls (41% for PYY(1-36), P = 0.04 and 32% for PYY(3-36), P = 0.02, median values).. Baseline plasma levels of PYY(1-36) or PYY(3-36) are markedly elevated in patients with renal failure undergoing peritoneal dialysis. Provocation studies disclose a marked disregulation in the postprandial secretion of these anorexigenic peptides, when compared with healthy controls. These findings may contribute to clarify the complex pathogenesis of anorexia of chronic renal failure.

Topics: Adult; Aged; Anorexia; Appetite; Case-Control Studies; Chronic Disease; Cross-Over Studies; Dialysis Solutions; Female; Food, Formulated; Glucose; Humans; Infusions, Parenteral; Male; Malnutrition; Middle Aged; Peptide YY; Peritoneal Dialysis; Renal Insufficiency

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients.

Topics: Adult; Anorexia; Appetite; Body Composition; Cardiovascular Diseases; Circadian Rhythm; Endocrine System Diseases; Energy Metabolism; Fasting; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Peptide YY; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency; Risk Factors