Ghrelin in cachexia associated with end-stage renal disease

Abstract

Much of the high mortality seen in chronic renal failure is due to a form of vascular disease which, unlike the overnutrition vascular disease of the general population, is closely associated with the development of malnutrition. Various micronutrient de fi ciencies occur, and are commonly treatment related, but a speci fi c syndrome of energy malnutrition associated with unexplained activation of in fl ammatory mediators, is a common and early feature of renal failure, which is frequently refractory to nutritional supplementation. Many abnormalities of appetite hormones have been found in renal failure, and like obesity, renal malnutrition is increasingly understood as a disorder of appetite homeostasis, which therefore would respond best to manipulation of the appetite regulatory system-for example by administration of ghrelin. Reduced clearance by failing kidneys leads to accumulation of ghrelin, with elevated circulating levels of total ghrelin; however, a reduction in the acyl fraction has been found. Acyl ghrelin administration has been shown to increase energy intake in animal models of renal failure, and promising results have also been found with daily subcutaneous injections in dialysis patients over the course of a week. In addition, ghrelin is thought to have an anti-in fl ammatory effect, which may be therapeutically relevant in a syndrome in which inappropriate in fl ammation is a prominent feature.