Pathogenic mechanisms underlying the variable response to recombinant human growth hormone in children with chronic renal failure.

As with spontaneous growth, the height gain achieved by stimulation with recombinant human growth hormone (rhGH) in children with chronic renal failure appears to be inversely related to the degree of renal dysfunction. The secondary complications of CRF that may independently interfere with growth, such as metabolic acidosis, anaemia, and secondary hyperparathyroidism, do not explain the poorer response to rhGH in children with end-stage renal failure. Certain abnormalities of the somatotropic hormone axis, the severity of which is related to the degree of renal dysfunction, are more likely to explain the dependence of the rhGH treatment response on glomerular filtration rate. These derangements include partial GH receptor deficiency, increased plasma binding of IGF-I, and accumulation of non-competitive inhibitors of IGF-I action. Strategies to optimise growth-promoting treatment in end-stage renal failure will depend on the relative contribution of these different somatotropic hormone axis alterations to uraemia.