Uremia reduces serum insulin-like growth factor i, increases insulin-like growth factor ii, and modifies their serum protein binding

Because uremia is associated with growth failure in children, serum levels of somatomedins have been studied in patients by bioassay, radioreceptor assay (RRA), and RIA. While bioassays have indicated low levels of somatomedin, RRA and RIA of native serum have been elevated. We reinvestigated this topic by insulin-like growth factor I (IGF-I) RIA and insulin-like growth factor II (IGF-II) specific rat placental membrane RRA. Sera were extracted with acid-ethanol, which recovers somatomedins and excludes somatomedin-binding proteins (SBP). Results are expressed as the relative potency compared to a normal human reference serum. The result of a serum IGF-I RIA of 22 adult patients undergoingchronic hemodialysis was 0.41 ± 0.05 U/ml (mean ± SE). Limits of normal adult sera are 0.58 and 1.84 U/ml. In contrast, the result of the IGF-II RRA was markedly elevated (3.9 ± 0.3 U/ml). Limits of normal adult serum are 0.39and 1.05 U/ml. To determine available serum binding protein, we incubated 2, 10, 25, and 100 μl of 7 uremic sera and 5 adult normal sera with [125I]IGF-II tracer in a total volume of 500 JU.1. After 16 h at 4 C, bound IGF was precipitated by 3 mg charcoal. The ratios of binding by uremic to normal sera were 4.29, 1.81, 1.58, and 1.41 at these 4 serum concentrations. The mean binding of IGF-II by uremic serum was elevated at all 4 concentrations. This increased binding could artifactually raise the apparent somatomedin concentrations in RRA and RIA of unextracted uremic serum. Sephadex G-200 filtrationrevealed an abnormality of IGF-I binding in uremia. In normal sera (n = 7), 27.8 ± 2.5% of IGF-I was present in a 50K component, the remainder was present in a 150K component. Five uremic sera had 51.4 ± 4.2% of IGF-I present as the50K component. We conclude that the uremic state is characterized by a reduced concentration of IGF-I (determined by RIA), markedly increased IGF-II (determined by RRA), and alterations in serum protein binding.