Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure.
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.
Frystyk
J
J
Medical Research Laboratory, Institute of Experimental Clinical Research, Aarhus UniversityHospital, and Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Aarhus N, Denmark. jan@frystyk.dk
Ivarsen
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Skjaerbaek
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Flyvbjerg
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Pedersen
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EB
Orskov
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D000328:Adult; D015153:Blotting, Western; D003404:Creatinine / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003404:Creatinine