Title:
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The use of recombinant human growth hormone in children with chronic renal failure
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The basis of this thesis is a multi-centre study looking at the safety and efficacy of the use of rhGH in 10 infants with chronic renal failure (CRF), 29 children with CRF, 14 children on peritoneal dialysis (PD), 8 on haemodialysis (HD) and 22 children following renal transplantation. All of the children were followed during one year of rhGH treatment except the transplanted children who were randomised either to receive 2 years of rhGH treatment or to receive no treatment in the first year and rhGH in the second year. RhGH treatment (liu/kg/week) improved short to medium term growth in all of these groups of children. Comparison between groups and factors predictive of the magnitude of response to rhGH are described, as are the effects of rhGH during the pubertal years. The main safety issues which are addressed are the effects of rhGH on renal function, immune function, renal bone disease, and the effects on glucose and lipid metabolism. Patients with acromegaly, where there is overproduction of GH, have large kidneys that have an increased glomerular filtration rate (GFR). In a setting of impaired renal function, a stimulus to increase GFR could result in hyperfiltration, which is thought to be one mechanism for progression of chronic renal impairment. Renal function was measured in the CRF and transplanted children; there was no significant change in the CRF group, but an increase was seen in the transplanted group after 1 week and 6 months which returned to baseline by one year. These findings and the effects of rhGH on blood pressure, renal size and protein excretion are discussed in detail. There are well established links between GH and the immune system, particularly in smaller mammals. In one man, GH and IGF-1 receptors are found on peripheral blood lymphocytes, and in vitro studies indicate a role for GH in lymphopoiesis and granulopoiesis. Minor changes in lymphocyte subsets have been reported with GH replacement in children with GH deficiency.
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