Volume 77, Issue 5, Pages 450-458 (March 2010) A super-agonist of growth hormone–releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease  Stanisław Niemczyk, Hanna Sikorska, Andrzej Więcek, Ewa Żukowska-Szczechowska, Klaudia Załęcka, 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  Kidney International  Volume 77, Issue 5, Pages 450-458 (March 2010) DOI: 10.1038/ki.2009.480 Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 1 Trial design and patient flow. DXA, dual-energy X-ray absorptiometry; GHRH, growth-hormone-releasing hormone; pt, patient. Kidney International 2010 77, 450-458DOI: (10.1038/ki.2009.480) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 2 Representative 24-h growth hormone concentration profiles at baseline (day 0/1, blue) and after 4 weeks of treatment (day 28/29; red). Left panel shows a patient from the placebo group; right panel shows a patient from the AKL-0707 group. The 24-h profiling was started at 0800 hours on day 0 and at 1230 hours on day 28. Injections were performed at 0800 and 1600 hours on day 28/29 profiles. GH, growth hormone. Kidney International 2010 77, 450-458DOI: (10.1038/ki.2009.480) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 3 Plasma concentrations of insulin-like growth factor 1 (IGF-1) and IGF-binding protein-1 and protein-3 before, during, and after treatment in 12 patients completing 4 weeks of treatment with AKL-0707 (red, squares) and in 14 patients completing 4 weeks of placebo administration (blue, circles). Nonparametric ANCOVA was used to assess differences between treatment groups in plasma IGF-1; ANOVA was used for repeated measurements to assess IGFBP-1 and IGFBP-3 differences (*P<0.05, **P<0.001, ***P<0.0001). ANOVA, analysis of variance; ANCOVA, analysis of covariance; IGFBP, insulin-like growth factor binding protein. Kidney International 2010 77, 450-458DOI: (10.1038/ki.2009.480) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 4 Changes in mean body weight, fat-free mass, and fat mass measured by dual-energy X-ray absorptiometry or bioimpedance during 4 weeks of either AKL-0707 (n=12) or placebo administration (n=14). Dashed red bars denote AKL-0707 and blue bars represent placebo. Asterisks (*) denote significant differences between treatment groups (*P<0.05, **P<0.01). BIA, bioimpedance; DXA, dual-energy X-ray absorptiometry; FFM, fat-free mass; FM, fat mass. Kidney International 2010 77, 450-458DOI: (10.1038/ki.2009.480) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 5 Subjective Global Assessment of nutritional status before and after 4 weeks of treatment with AKL-0707 or placebo. The change in nutritional status differed significantly between treatment groups (P<0.01). Kidney International 2010 77, 450-458DOI: (10.1038/ki.2009.480) Copyright © 2010 International Society of Nephrology Terms and Conditions