Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment

Abstract

Malnutrition is a common complication in patients on dialysis and is strongly associated with poor prognosis. Effective therapy could substantially improve morbidity and mortality, but neither enteral nor parenteral supplementation provide long-term benefit because of the strong appetite suppression seen in such patients. We performed a double-blinded randomized crossover study of a week-long treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger through the hypothalamus, in a group of 12 malnourished dialysis patients. Ghrelin administration increased ghrelin levels in circulation, modestly reduced blood pressure for up to 2 h, and immediately and significantly increased appetite, with an increase in energy intake noted at the first study meal. Persistence of this effect throughout the week was confirmed with food diaries and final study meals. Energy expenditure, measured with free-living pulse and motion monitors, was unchanged by ghrelin. Our study shows that daily treatment with ghrelin achieves a sustained positive change in energy balance in malnourished dialysis patients. Direct manipulation of appetite with ghrelin or its analogs represents an attractive and promising therapeutic strategy for this difficult clinical problem.

The hunger hormone ghrelin in cachexia

“…The same positive result has also been obtained in a 7-day trial, showing that in malnourished dialysis patients' daily subcutaneous ghrelin injection significantly improved appetite, with an increase in energy intake observed at the first study meal without side effects throughout the whole week of clinical observation [16]. Also, energy expenditure, evaluated with free-living pulse and motion monitors, was not influenced by ghrelin administration [16]. In an animal model of chronic renal failure, ghrelin infusion resulted in increased food intake and an improvement in body composition related in part to a decrease in muscle protein breakdown [17].…”

“…In a small clinical study, aimed at evaluating the effects of subcutaneous administration of ghrelin in mild and moderate malnourished peritoneal dialysis patients, oral energy intake immediately doubled [15]. The same positive result has also been obtained in a 7-day trial, showing that in malnourished dialysis patients' daily subcutaneous ghrelin injection significantly improved appetite, with an increase in energy intake observed at the first study meal without side effects throughout the whole week of clinical observation [16]. Also, energy expenditure, evaluated with free-living pulse and motion monitors, was not influenced by ghrelin administration [16].…”

Association of Plasma Des-acyl Ghrelin Levels with CKD

“…Ghrelin has potent orexigenic activity and induces an increase in food intake, and muscle mass with a positive change in energy uremic balance in rats (32)(33)(34). Ghrelin administered to dialysis patients increased appetite and food intake, induced a sustained positive change in energy balance (35,36) and increased food intake in malnourished patients on peritoneal dialysis (35). Thus, a decrease in AG in CKD could theoretically play a role in the malnutrition observed in many of these patients.…”

A Patient with CKD and Poor Nutritional Status

“…Ghrelin is an orexigenic peptide released primarily from the stomach; it increases appetite and adjusts both short-and long-term energy balance, making it a good candidate for treatment of anorexic patients with ESRD. Two pilot studies suggested improved energy intake during short-term ghrelin administration (72,73). There is also limited but supportive evidence for the effectiveness of pre-and probiotics on reducing plasma levels of some uremic toxins (74).…”