Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia

Pediatr Nephrol. 1991 Jul;5(4):539-44. doi: 10.1007/BF01453697.


Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF, n = 31) and chronic renal failure (n = 11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity cross-linking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12-20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production.

MeSH terms

  • Adolescent
  • Carrier Proteins / blood
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / pharmacology*
  • Child
  • Child, Preschool
  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Glomerular Filtration Rate
  • Growth Hormone / pharmacology*
  • Humans
  • Infant
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / antagonists & inhibitors
  • Insulin-Like Growth Factor II / metabolism
  • Kidney Failure, Chronic / metabolism
  • Radioimmunoassay
  • Somatomedins / antagonists & inhibitors*
  • Somatomedins / metabolism
  • Uremia / metabolism*


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Growth Hormone