DECREASED BIOAVAILABILITY OF INSULIN-LIKE GROWTH-FACTOR-I, A CAUSE OFCATABOLISM 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 IG F-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemod ialysis on low flux filters. IGF-I, insulin and IGFBP-1 were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitome try after Western ligand blotting. Diurnal curves of IGFBP-1 were perf ormed in two additional patients. Before dialysis, the mean (+/-SEM) I GF-I level was 202.2+/-12.1 ug/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 ug/l) and increased further during hemodialysis to 118.1+/-28 .5 ug/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 refe rence serum and was not significantly changed by dialysis. The predial ysis IGPBP-3, 38.5 kDa band was within normal levels 90.1+/-18.8% of t he reference serum while the IGFBP-3, 41.5 kDa band was decreased to 6 2.4+/-11.3% of the reference serum. Both IGFBP-3 bands were not signif icantly 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 unchan ged after dialysis. The ratio between IGF-I and IGFBP-1 decreased sign ificantly 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-dialys is day. In ESRD patients predialysis mean values of insulin, IGF-I SD- score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometr ic values of the IGFBP-3 bands on Western ligand blot were either norm al or reduced. IGFBP-1 was raised significantly with a mean of 74% aft er 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.