Decreased bioavailability of insulin-like growth factor-I, a cause of catabolism in hemodialysis patients?
The aim of this study was to investigate the influence of hemodialysis on insulin-like growth factor-I (IGF-I) and the IGF binding proteins (IGFBPs) in patients with end-stage renal disease (ESRD). IGF-I and IGF-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemodialysis on low flux filters. IGF-I, insulin and IGFBP-I were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitometry after Western ligand blotting. Diurnal curves of IGFBP-1 were performed in two additional patients. Before dialysis, the mean (+/- SEM) IGF-I level was 202.2 +/- 12.1 micrograms/l corresponding to a SD-score of 1.8 +/- 0.3. Basal IGFBP-1 was increased 2-fold compared to normal levels (82.4 +/- 24.1 micrograms/l) and increased further during hemodialysis to 118.1 +/- 28.5 micrograms/l (P < 0.007). The mean increase during dialysis in IGFBP-1 was 74 +/- 24%. Predialysis IGFBP-2 was increased to 184.8 +/- 32.5% of the reference serum and was not significantly changed by dialysis. The predialysis IGFBP-3, 38.5 kDa band was within normal levels 90.1 +/- 18.8% of the reference serum while the IGFBP-3, 41.5 kDa band was decreased to 62.4 +/- 11.3% of the reference serum. Both IGFBP-3 bands were not significantly changed after dialysis. The mean basal insulin level was high, 38.2 +/- 3.0 mU/L, in spite of normal glucose levels suggesting insulin resistance. The mean values of IGF-I, insulin and glucose were unchanged after dialysis. The ratio between IGF-I and IGFBP-1 decreased significantly after dialysis to 53% of the ratio before dialysis (P < 0.005). The ratio between IGF-I and IGFBP-2 or IGFBP-3 did not change after dialysis. The circadian variation of IGFBP-1 during dialysis days was impaired with a delayed decrease of IGFBP-1 compared to the non-dialysis day. In ESRD patients predialysis mean values of insulin, IGF-I SD-score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometric values of the IGFBP-3 bands on Western ligand blot were either normal or reduced. IGFBP-1 was raised significantly with a mean of 74% after dialysis, the predialysis level was more than 2-fold elevated with impaired circadian variation of IGFBP-1 on dialysis days. High levels of IGFBPs may bind free IGF-I and decrease IGF-I bioavailability thus contributing to the catabolism associated with dialysis.
Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden.
B F
BF
Lindgren
I
I
Odar-Cederlöf
F
F
Ericsson
K
K
Brismar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012044:Regression Analysis; D006435:Renal Dialysis; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000378:metabolism
D001786:Blood Glucose; 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; D018969:Insulin-Like Growth Factor Binding Proteins; D012709:Serum Albumin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II