Characterization of urinary insulin-like growth factor binding proteins.

The insulin-like growth factors (IGFs) are important mitogens that are present in many body fluids, where they are commonly bound with high affinity to IGF binding proteins (IGFBPs). We investigated human urine for the presence of IGFBPs. Western ligand blots of concentrated, dialyzed normal urine disclosed the presence of two major bands with IGF binding activity, one at 40-44 kilodaltons and another at 31 kDa. Deglycosylation with endoglycosidase F, and immunoprecipitation with alpha HEC1 antibody revealed these proteins to be hIGFBP-3 and hIGFBP-2, respectively. Comparison of IGFBPs in normal serum and urine showed a reversal of the hIGFBP-2/hIGFBP-3 ratio in urine compared to serum, with hIGFBP-2 being the predominant binding protein in normal urine. The 150 kDa form of hIGFBP-3 was absent in normal urine. In patients with renal disease, the urinary IGFBP (U-IGFBP) pattern was altered. Patients with glomerular disease and proteinuria had elevated U-hIGFBP-3, whereas patients with renal failure who displayed increased urinary beta-2-microglobulin had a dramatic increase in U-hIGFBP-1, in the face of normal serum IGFBP profiles. In conclusion, we have documented the presence of IGFBPs in the urine of normal and diseased individuals. The presence of IGFBPs in urine may complicate the assessment of IGF measurements in urine. U-IGFBPs may be potential clinical markers in renal diseases. Additional studies are required before the origin of urinary IGFBPs in both normal and pathological conditions will be definitively established.