The use of recombinant human growth hormone in short children with chronic renal failure.
Regulation of the somatotropic axis is altered in chronic renal failure (CRF) resulting in a secondary syndrome of growth hormone (GH) insensitivity. Secretion of growth hormone estimated by deconvolution analysis is low normal in prepubertal patients and reduced in late pubertal children with CRF. Basal and integrated GH serum concentration measured by RIA is increased due to reduced renal metabolic clearance, whereas the fractional urinary excretion is increased due to damage of renal tubular cells. GH receptor mRNA is decreased (rat) and the serum concentration of GH binding protein (BP) activity is low (man). Insulin-like growth factor (IGF)-1 production rate is reduced, whereas serum concentrations of IGFBPs are increased secondary to reduced renal metabolic clearance. This results in a reduction of free, active IGF-1. Treatment with GH induces a rise in serum IGF-1 concentration and normalizes IGF bioactivity. Clinical studies in prepubertal children demonstrated a dramatic rise in height velocity during the first treatment year and to a lesser extent during the following years. In children on conservative treatment prior to dialysis, mean height SDS improved by 1.5 within two years and by 2.0 within four years. Patients with renal allografts responded in a similar way. Age and pretreatment height velocity SDS are confounding variables for the response to GH. Renal function seems not be altered by recombinant human (rh) GH in patients with CRF, and the number of renal allograft rejection crises seems not to be substantially increased under rhGH treatment in allograft recipients.
Mehls
O
O
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Tönshoff
B
B
Haffner
D
D
Wühl
E
E
Schaefer
F
F
D002648:Child; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D013006:Growth Hormone