Growth hormone, insulin-like growth factors and their binding proteins in adult hemodialysis patients treated with recombinant human growth hormone

Background: Growth deficiency and malnutrition in uremic children are often caused by malfunction of the growth hormone (GH)/insulin-like growth facto r I (IGF-I) axis and can be corrected by treatment with GH. The purpose of this study was to evaluate the levels of GH, IGF-I and II and their binding proteins compared to changes in body composition in adult, enfeebled, urem ic patients in chronic hemodialysis (HD), treated for 6 months with recombi nant human growth hormone (rhGH). Methods: 31 patients were included in a c ontrolled, randomized, double-blinded study using either 4 IU/m(2)/day of r hGH or placebo injected subcutaneously every evening for 6 months. Results: Fasting levels of GH were normal at start and increased significantly from 2.2 to 13.5 mu g/l (p = 0.01) within the first 4 months of rhGH treatment. Before treatment IGF-I was at the upper limit of normal range (130 to 220 mu g/l) in both groups, and it increased significantly from 213 to 348 mu g /l (p = 0.01) during rhGH treatment. IGF-II was above the normal range in b oth groups, and remained unchanged throughout. IGFBP-1 decreased in the rhG H treated group from 53.1 to 24.7 mu g/l (p = 0.004), while IGFBP-3 increas ed from 5620 to 7100 mu g/l (p = 0.004). The molar ratio of IGF-I/IGFBP-3 i ncreased significantly from 14 to 25 % (p = 0.01), while the ratio decrease d in the placebo group (p = 0.01). During the treatment with rhGH the patie nts increased their lean body mass (= muscle mass) by a median of 3.18 kg ( range 0.82 to 5.12 kg) (p = 0.0001) while their fat mass decreased by a med ian of 3.33 kg (range 0.18 to 5.82 kg) (p = 0.004). Total body mass (= weig ht) remained stable. No significant changes were observed in the placebo gr oup. Conclusion: The baseline GH and IGF-I concentrations were normal in ma lnourished HD patients. When treated with rhGH in a dosage as used in growt h-retarded uremic children, IGF-I increased to the levels seen in acromegal ic persons. IGF-I increased more than IGFBP-3 whereby its biological activi ty obviously improved. This was reflected in an increased muscle mass and a decreased fat mass. The rhGH treatment was well tolerated.