Disturbance of growth hormone--insulin-like growth factor axis in uraemia. Implications for recombinant human growth hormone treatment.
The growth hormone/insulin-like growth factor (IGF) axis is disturbed in uraemia. Elevated plasma growth hormone (GH) levels despite diminished growth suggest GH resistance, which may be due in part to a decreased expression of the growth hormone receptor at the cell membrane. The hepatic production of IGFs under the control of GH is impaired. Furthermore, there is an excess of IGF-binding protein over total IGF as a consequence of reduced renal clearance of low-molecular-weight subunits of the IGF-binding protein (IGF-BP). This results in an absolute (diminished production) and a relative (low bioavailability) deficiency of IGF. Recombinant human growth hormone (rhGH) in doses of 4 IU/m2 per day is able to induce catch-up growth in children with preterminal and terminal renal failure. The growth stimulation of exogenous GH is attributed to its potency to increase the ratio of IGF-I to IGF-BP, followed by a normalization of IGF bioactivity. In renal transplanted children growth is not only disturbed by decreased renal function but also by steroid treatment. Corticosteroids are responsible for catabolism, for suppression of pituitary GH secretion and for inhibition of local production of IGFs. Exogenous rhGH is able to counteract these growth-inhibiting effects. However, it remains to be seen whether long-term GH treatment definitely improves final adult height.
Tönshoff
B
B
Division of Paediatric Nephrology, University Children's Hospital, Heidelberg, Federal Republic of Germany.
Schaefer
F
F
Mehls
O
O
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006130:Growth Disorders / Q000188:drug therapy / Q000503:physiopathology; D013006:Growth Hormone / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D010902:Pituitary Gland / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D013002:Somatomedins / Q000378:metabolism*; D014511:Uremia / Q000188:drug therapy / Q000378:metabolism*
D011994:Recombinant Proteins; D013002:Somatomedins; D013006:Growth Hormone