Growth, growth axis and body composition before and after use of growth hormone in children with chronic renal failure.

The studies in this thesis were designed to elucidate the role of clinical and endocrinological factors in the growth suppression that is a recognised feature of chronic renal failure (CRF) and renal transplantation, and to determine whether the mechanism of action of recombinant growth hormone (rhGH) is by improving endocrine disturbances or via a direct anabolic effect. Endocrine parameters (IGF-I, IGF-II, IGF bioactivity, IGFBP-1, IGFBP-2, IGFBP-3, ALS, insulin and c-peptide) were studied in 3 groups of children - those with renal transplants and those with reduced glomerular filtration rate (GFR), moderate and severe. Clinical variables (age, gender, body mass index - BMI), aetiology of renal failure, steroid dose and renal modality - (CRF/ transplant/ dialysis) were also included in the analysis. All 3 groups had elevated mean IGF-II, IGFBP-2 and -3 levels. IGF-I levels, although in the normal range, would be considered low in this population as GH levels are elevated. IGF-II and ALS had a significant positive influence on growth, whilst renal modality, age, steroid treatment and duration of dialysis all had a significantly negative effect. Collectively these parameters explained 38.4% of the variability in height (Ht) standard deviation score (SDS) in the population studied. Of all the parameters studied, only transplantation had a significant influence on Ht velocity (Vel) SDS. This was positive and accounted for 26% of the variability in Ht Vel SDS. Protein turnover was measured in 8 fasting children (4 CRF, 4 transplant) using stable isotopes (13C) incorporated into leucine. Turnover was lower at baseline, and remained so despite any increases with rhGH treatment, in transplanted children compared with those with CRF. The body mass index of transplanted children who were on steroid treatment was higher, but their resting energy expenditure (REE) was lower than CRF patients. RhGH improved growth rate, arm muscle area and REE significantly whilst fat area decreased. C-peptide and IGFBP-3 showed a more consistent increase than IGF-I whilst IGFBP-1 decreased with rhGH. The studied parameters can only partially explain the observed variability in growth rate suggesting the involvement of other factors. RhGH has anabolic effects which are apparent despite variation in endocrine responses between individuals. This variation could be attributed to differing levels of resistance to the actions of hormones