Eating Behavior Disorders in Uremia: A Question of Balance in Appetite Regulation

Abstract

Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to "inadequate" dialysis as judged by uncertain means ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and others). We propose the tryptophan-serotonin hypothesis, based on a uremia-induced disorder in patients' amino acid profile--low concentrations of large neutral and branched-chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood-brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin-like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3 adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched-chain amino acids.

Gastrointestinal Symptoms and Nutritional Status in Women and Men on Maintenance Hemodialysis

“…[46][47][48][49][50] If effective interventions are targeted to MHD patients most in need, they are likely to narrow the female-male gaps in gastrointestinal symptoms and nutritional status. [46][47][48][49][50] Nausea, vomiting, and reduced appetite in patients with chronic renal failure may be related to the intake of specific types of foods. 48,49 Moreover, the susceptibility to nausea and vomiting seems to be more strongly related to aversion to certain types of foods in women than in men.…”

Kidney–brain crosstalk in the acute and chronic setting

“…129 This clinical situation is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid that can promote a high level of tryptophan transport across the blood-brain barrier, enhance the synthesis of 5-hydroxytryptamine, and results in a reduction in appetite. 130 Furthermore, elevated concentrations of proinflammatory cytokines, such as leptin, free tryptophan, and 5-hydroxytryptamine in the cerebrospinal fluid, combined with a lack of neural nitric oxide and disorders in receptors such as melanocortin receptor-4, can further contribute to anorexia in the uraemic state. 129 Other consequences of uraemia on CNS function Studies using rat models of uraemia have demonstrated that increases in cytosolic calcium levels within synaptosomes are mediated by parathyroid hormone.…”

Insulin resistance and cancer: the role of insulin and IGFs

“…For instance, H. pylori has been reported to confer protective effects against esophageal cancer (Islami & Kamangar 2008), but on the other hand, together with hepatitis B and C viruses, and human papillomaviruses, the bacterium is responsible for about a third of all cancers attributable to infections, mainly including gastric, liver, and cervix uteri cancers (de Martel et al 2012, Sakitani et al 2012. In addition, silent infection with H. pylori is a source of pro-inflammatory cytokines and IGF1 in hyperinsulinemia conditions (Aguilera et al 2004, Ozen et al 2011. Unraveling the precise role of ILP molecules in H. pylori-related carcinogenesis may provide novel pharmacological targets for microorganism-related cancers.…”