IGF-binding protein-3 fragments in plasma of a child with acute renal failure.

The insulin-like growth factors (IGF) -I and -II promote cellular growth and differentiation of various organs. Their growth-stimulating effects are modulated by a family of six IGF-binding proteins (IGFBPs). Altered patterns of intact and fragmented IGFBPs have been reported in serum and urine of children with chronic renal failure (CRF), and it has been suggested that this may contribute to the growth failure observed in these patients. In the present study, a rapid and comprehensive method is presented to analyze IGFBPs and IGFBP fragments in the plasma of a child with acute renal failure (ARF) who had undergone plasmapheresis. The plasma IGF-I and IGFBP-3 levels were drastically reduced. Plasmapheresis filtrate (3 l) was fractionated by cation-exchange chromatography and reversed-phase high-performance liquid chromatography. The fractions obtained were tested by ligand and immunoblotting. In addition to IGFBP-1 and -4 fragments, the majority of IGF-binding polypeptides were IGFBP-3 immunoreactive. N-terminal sequence analysis of a 17-kDa polypeptide revealed the isolation of a C-terminal fragment of IGFBP-3 starting with Lys 160. The IGF-II-binding polypeptide pattern in the ARF plasma resembles the pattern in hemofiltrate from CRF patients, suggesting that similar or identical proteases are involved in IGFBP-3 fragmentation and common mechanisms may lead to the accumulation of the fragments in both diseases.