Unacylated Ghrelin: A Novel Regulator of Muscle Intermediate Metabolism With Potential Beneficial Effects in Chronic Kidney Disease

In patients with chronic kidney disease (CKD), malnutrition with loss of skeletal muscle mass has a negative impact on morbidity and mortality. Emerging evidence indicates that a cluster of oxidative stress, inflammation, and insulin resistance directly contributes to skeletal muscle catabolism by favoring protein breakdown over synthesis. Ghrelin is a gastric hormone discovered and initially studied in its acylated orexigenic form. More recently, a role of unacylated ghrelin (UnAG) has been described to reduce skeletal muscle mitochondrial reactive oxygen species generation, inflammation, and insulin resistance both in experimental models and in clinical studies. UnAG administration could therefore represent a potential comprehensive therapeutic approach for CKD-related metabolic and nutritional complications. Studies of UnAG administration in experimental and clinical CKD are needed to test the hypothesis that UnAG may chronically improve nutritional status and outcome in CKD patients.