title: A super-agonist of growth hormone-releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease.
abstract: Chronic kidney disease is frequently associated with protein-energy wasting related to chronic inflammation and a resistance to anabolic hormones such as insulin and growth hormone (GH). In this study, we determined whether a new GH-releasing hormone super-agonist (AKL-0707) improved the anabolism and nutritional status of nondialyzed patients with stage 4-5 chronic kidney disease randomized to twice daily injections of the super-agonist or placebo. After 28 days, this treatment significantly increased 24-h GH secretion by almost 400%, without altering the frequency or rhythmicity of secretory bursts or fractional pulsatile GH release, and doubled the serum insulin-like growth factor-1 level. There was a significant change in the Subjective Global Assessment from 'mildly to moderately malnourished' to 'well-nourished' in 6 of 9 patients receiving AKL-0707 but in none of 10 placebo-treated patients. By dual-energy X-ray absorptiometry, both the mean fat-free mass and the body mineral content increased, but fat mass decreased, all significantly. In the AKL-0707-treated group, both serum urea and normalized protein equivalent of nitrogen appearance significantly decreased with no change in dietary protein intake, indicating a protein anabolic effect of treatment. Thus, our study shows that stimulation of endogenous GH secretion by AKL-0707 overcomes uremic catabolism of patients with advanced chronic kidney disease.
authors.affiliation: Department and Clinic of Nephrology, Dialysis, and Internal Medicine, Warsaw University of Medicine, Banacha Hospital, Warsaw, Poland.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Niemczyk
authors.forename: Hanna
authors.initials: H
authors.lastname: Sikorska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiecek
authors.forename: Ewa
authors.initials: E
authors.lastname: Zukowska-Szczechowska
authors.forename: Klaudia
authors.initials: K
authors.lastname: Załecka
authors.forename: Joanna
authors.initials: J
authors.lastname: Gorczyńska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kubik
authors.forename: Beata
authors.initials: B
authors.lastname: Czerwieńska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gosek
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: David A
authors.initials: DA
authors.lastname: Wagner
authors.forename: Pierrette
authors.initials: P
authors.lastname: Gaudreau
authors.forename: Tiina
authors.initials: T
authors.lastname: Hakonen
authors.forename: Sam Wai Kit
authors.initials: SW
authors.lastname: Kay
authors.forename: Taneli
authors.initials: T
authors.lastname: Jouhikainen
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D013007:Growth Hormone-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C549379:AKL-0707; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone