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: Stanisław Niemczyk, Hanna Sikorska, Andrzej Wiecek, Ewa Zukowska-Szczechowska, Klaudia Załecka, Joanna Gorczyńska, Małgorzata Kubik, Beata Czerwieńska, Katarzyna Gosek, Johannes D Veldhuis, David A Wagner, Pierrette Gaudreau, Tiina Hakonen, Sam Wai Kit Kay, Taneli Jouhikainen, Franz Schaefer
• Journal: Kidney international (Kidney Int) Vol. 77 Issue 5 Pg. 450-8 (Mar 2010) ISSN: 1523-1755 [Electronic] United States
• PMID: 20016461 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AKL-0707
• Human Growth Hormone
• Insulin-Like Growth Factor I
• Growth Hormone-Releasing Hormone

Topics

• Aged
• Double-Blind Method
• Female
• Follow-Up Studies
• Growth Hormone-Releasing Hormone (agonists, analogs & derivatives, therapeutic use)
• Human Growth Hormone (metabolism)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Kidney Failure, Chronic (drug therapy)
• Male
• Middle Aged
• Nutritional Status (drug effects)
• Time Factors
• Treatment Outcome