Measurement of free GH and bioactive IGF-I in non-diabetic haemodialysis patients treated with GH for 7 days

作者：Frystyk Jan^*; Djurhuus Christian Born; Johansen Thue; Lange Martin; Smidt Kamille; Christiansen Jens Sandahl

来源：Nephrology Dialysis Transplantation, 2012, 27(11): 4211-4218.

DOI：10.1093/ndt/gfs364

• free GH
• bioactive IGF-I
• ultrafiltration
• GHBP
• GH resistance

End-stage renal failure (ESRF) patients demonstrate augmented growth hormone (GH) secretion, but normal insulin-like growth factor-I (IGF-I) concentrations, indicating a state of GH resistance. To test this hypothesis, we compared the IGF-I response with exogenous GH in haemodialysis patients and healthy controls, with special focus on free GH and bioactive IGF-I. %26lt;br%26gt;Ultrafiltered free GH and total GH were measured in serum collected hourly for 24 h at baseline and after 7 days of recombinant human (rh) GH (50 g/kg/day) treatment in 11 non-diabetic haemodialysis patients and 10 matched controls. Serum levels of bioactive IGF-I (determined by cell-based IGF-I receptor activation assay), total IGF-I and the GH-binding protein (GHBP) were assayed twice daily. %26lt;br%26gt;At baseline, patients showed elevated total GH (24 5 versus 9 1 g/L h, P 0.02), free GH (21 5 versus 7 1 g/L h, P 0.02), reduced GHBP (1.5 0.3 versus 2.5 0.2 nmol/L, P 0.01), high-normal total IGF-I (173 18 versus 135 14 g/L, P 0.12) and subnormal bioactive IGF-I (2.1 0.3 versus 2.8 0.2 g/L, P 0.05) when compared with controls. After 7 days of rhGH treatment, there was a greater GH increase in the non-diabetic haemodialysis patients than in controls (total GH: 293 33 versus 166 13 g/L h, P 0.001; free GH: 284 40 versus 126 15 g/L h, P 0.001). GHB remained unaffected and total IGF-I increased to the same extent in patients and controls (701 87 versus 572 33 g/L, P 0.17), whereas bioactive IGF-I tended to be lower in patients (5.37 0.55 versus 6.63 0.25 g/L, P 0.10). When adjusting for the actual increments in plasma GH, the ability of exogenous GH to stimulate bioactive IGF-I levels was reduced by approximate to 50 in ESRF (P 0.02), whereas the response of total IGF-I remained normal (74; P 0.18) %26lt;br%26gt;The study demonstrates that ESRF is associated with markedly elevated serum levels of free GH. Furthermore changes in bioactive, but not immunoreactive, IGF-I indicated that the hepatic sensitivity to GH was reduced by 50 in ESRF patients. Clearly, the physiological importance of our observations awaits further studies, but they suggest that changes in total IGF-I may not necessarily reflect changes in the endogenous activity of IGF-I in ESRF patients on GH treatment.