A super-agonist of growth hormone-releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease.
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.
Niemczyk
Stanisław
S
Department and Clinic of Nephrology, Dialysis, and Internal Medicine, Warsaw University of Medicine, Banacha Hospital, Warsaw, Poland.
Sikorska
Hanna
H
Wiecek
Andrzej
A
Zukowska-Szczechowska
Ewa
E
Załecka
Klaudia
K
Gorczyńska
Joanna
J
Kubik
Małgorzata
M
Czerwieńska
Beata
B
Gosek
Katarzyna
K
Veldhuis
Johannes D
JD
Wagner
David A
DA
Gaudreau
Pierrette
P
Hakonen
Tiina
T
Kay
Sam Wai Kit
SW
Jouhikainen
Taneli
T
Schaefer
Franz
F
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
C549379:AKL-0707; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone