Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation

Abstract

Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.

Effects of growth hormone on growth factors after renal transplantation

“…In the present study, we examined sequential IGF and IGFBPs in ten transplanted children that received recombinant human GH (rhGH) treatment for 1 year at a mean time after transplantation of about 3 years, at variance with the previously reported study [12]. The aim of this study was to determine the long-term effects of GH on IGF/IGFBPs in a stable post-transplant period and to investigate the possible role of these parameters in the growth response.…”

“…Only one [12] described the effects of 2 years GH treatment on IGF/IGFBPs in three short children that received a transplant during GH therapy. In these conditions the authors reported an elevated IGF-1 level before transplantation that remained increased after transplantation.…”

The Insulin-Like Growth Factor System in Kidney Diseases

“…In contrast, the IGFBP-1 level was reported to decrease with GH therapy after transplantation. The effect of lowering the serum levels of IGFBPs may be associated with enhancing the IGF bioactivity and hence associated with an increase in growth velocity [33, 34]. …”

United Network for Organ Sharing rules and organ availability for children: Current policies and future directions

“…Growth failure may also be accompanied with specific nutritional deficiencies as well as protein calorie malnutrition. Poorly growing children with chronic liver and renal failure have well‐described perturbations in the growth hormone and insulin growth factor axes (3–5).…”