Hormones – Cytokines – Signaling
Kidney International (1999) 56, 2076–2084; doi:10.1046/j.1523-1755.1999.00798.x
Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure
Jan Frystyk, Per Ivarsen, Christian Skjærbæk, Allan Flyvbjerg, Erling Bjerregaard Pedersen and Hans Ørskov
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, and Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Aarhus N, Denmark; and Holstebro Hospital, Holstebro, Denmark
Correspondence: Dr Jan Frystyk, Institute of Experimental Clinical Research, Aarhus Kommune Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. E-mail:jan@frystyk.dk
Received 12 April 1999; Revised 22 July 1999; Accepted 3 August 1999.
Abstract
Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure.
Background
Chronic renal failure (CRF) results in major changes in the circulating growth hormone (GH)/insulin-like growth factor (IGF) system. However, there are only limited data on changes in free IGF-I in CRF.
Methods
Matched groups of nondiabetic, nondialyzed patients with CRF (N = 25) and healthy controls (N = 13) were compared. The creatinine clearance (CCr) based on a 24-hour urine collection ranged from 3 to 59 and 89 to 148 ml/min/1.73 m2 in patients and controls, respectively. Overnight fasting serum samples were analyzed for free and total IGF-I and -II, and IGF-binding protein (IGFBP)-1, -2, and -3. Additionally, intact as well as proteolyzed IGFBP-3 was determined.
Results
The patients had reduced serum-free IGF-I (-53%) and increased levels of total IGF-II (40%), IGFBP-1 (546%), and IGFBP-2 (270%, P < 0.05). Serum total IGF-I and free IGF-II were normal. Also, serum levels of immunoreactive IGFBP-3 were elevated (33%, P < 0.05), but this could be explained by an increased abundance of IGFBP-3 fragments, as ligand blotting showed no difference in levels of intact IGFBP-3. Accordingly, patients had an increased proteolysis of IGFBP-3 in vivo (17%) and in vitro (7%, P < 0.05). In patients, free IGF-I levels correlated positively with CCr (r2 = 0.38, P < 0.002) and inversely with IGFBP-1 (r2 = 0.69, P < 0.0001) and IGFBP-2 (r2 = 0.41, P < 0.0007), whereas CCr was inversely correlated with levels of IGFBP-1 (r2 = 0.48, P < 0.0001) and IGFBP-2 (r2 = 0.63, P < 0.0001).
Conclusions
These data strongly support the hypothesis that CRF-related growth failure and tissue catabolism are caused by an increased concentration of circulating IGFBP-1 and -2, resulting in low serum levels of free IGF-I and thus IGF-I bioactivity. In addition, low levels of free IGF-I may explain the increased secretion of GH in CRF.
Keywords:
growth hormone, tissue catabolism, end-stage renal failure, creatinine clearance
