Subcutaneous Ghrelin Enhances Acute Food Intake in Malnourished Patients Who Receive Maintenance Peritoneal Dialysis

Abstract

Anorexia and malnutrition confer significant morbidity and mortality to patients with end-stage kidney disease but are resistant to therapy. The aim of this study was to determine whether subcutaneous administration of ghrelin, an appetitestimulating gut hormone, could enhance food intake in patients who are receiving maintenance peritoneal dialysis and have evidence of malnutrition. The principal outcome measure was energy intake during a measured study meal. Secondary outcome measures were BP and heart rate and 3-d food intake after intervention. Nine peritoneal dialysis patients with mild to moderate malnutrition (mean serum albumin 28.6 ؎ 5.0 g/L, total cholesterol 4.4 ؎ 0.6 mmol/L, subjective global assessment score of 5.7 ؎ 1.7) were given subcutaneous ghrelin (3.6 nmol/kg) and saline placebo in a randomized, double-blind, crossover protocol. Administration of subcutaneous ghrelin significantly increased the group mean absolute energy intake, compared with placebo, during the study meal (690 ؎ 190 versus 440 ؎ 250 kcal; P ‫؍‬ 0.0062). When expressed as proportional energy increase for each individual, ghrelin administration resulted in immediate doubling of energy intake (204 ؎ 120 versus 100%; P ‫؍‬ 0.0319). Administration of ghrelin maintained a nonsignificant increase in energy intake over 24 h after intervention (2009 ؎ 669 versus 1579 ؎ 330 kcal) and was not followed by subsequent underswing (1790 ؎ 370 versus 1670 ؎ 530 and 1880 ؎ 390 versus 1830 ؎ 530 kcal on days 2 and 3, respectively). Ghrelin administration resulted in a significant fall in mean arterial BP (P ‫؍‬ 0.0030 by ANOVA). There were no significant adverse events during the study. Subcutaneous ghrelin administration enhances short-term food intake in dialysis patients with mild to moderate malnutrition.

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.…”

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

“…The immediate increase in energy intake in those patients was followed by a trend toward increased energy intake over the following 24 hours. In addition, there was no subsequent compensatory reduction in energy intake over the following 3 days, which would negate any potential therapeutic benefit of subcutaneous ghrelin administration [65].…”

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).…”