Search

Few publications have described the long-term effects of recombinant human growth hormone (rhGH) in uremic patients. This study reports the results of rhGH therapy at the end of treatment and at adult age in 178 French patients. At enrollment, 63 patients were under conservative treatment (CT), 40 under hemodialysis (HD), and 75 had a functioning renal transplant (RT). Under rhGH treatment, height velocities (HV) significantly increased in all patients, but the effect was significantly better in the CT group. The HV gain (HV under rhGH-HV before treatment) was similar in all three groups. Increases in HV allowed height standard deviation scores (SDS) catch up, and this effect persisted over a 5-year period. SDS height at the completion of treatment was significantly related to group (best in CT) and response to treatment during the first year. Data on adult height was available for 102 patients. Mean adult height was 162.2 cm in men and 152.9 cm in women, and 46% were > −2 SDS for height. Adult height SDS was correlated with height SDS and spontaneous HV before treatment and effect of treatment. Analysis of adult height in the 49 patients who entered the protocol with a height SDS between −2 and −3 (the current recommendation for rhGH use) revealed that 65% had an adult-height SDS >−2. These adult heights were significantly better if compared with historical cohorts of patients not treated by rhGH; rhGH significantly improves the adult-height prognosis of uremic patients suffering from growth retardation. Early rhGH administration during CT gives better height SDS at both the end of rhGH therapy and in adulthood. [ABSTRACT FROM AUTHOR]

According to the analysis of the Collaborative Transplant Study (CTS), the incidence of renal carcinoma in patients with renal transplantation as well as with heart transplantation is significantly increased at any given patient age. The cumulative incidence 10 years after kidney transplantation is 185 per 100,000 patients in children below the age of 19 years at the time of transplantation. Age and immunosuppressive treatment seem to be the major risk factors. The majority of cancers develop within the native kidneys. Chronic transplant nephropathy and accelerated senescence may be further risk factors for the development of cancer within a kidney transplant. Growth hormone (GH) treatment could not be identified as an additional risk factor. [ABSTRACT FROM AUTHOR]

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4±1.1 years and a mean bone age (BA) of 7.3±0.9 years. Mean height was –3.9±0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9±0.6 and the mean inulin clearance was 36.5±4.9 ml/min/1.73 m[sup 2] . Recombinant hGH was given at 4 IU/m[sup 2] /day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P<0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P<0.01) by about 100% (mean values after GH therapy: 95.9± 2.1 nM and 165±29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148±18 pM, P<0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0 standard deviation score (SDS) for age, were selected to receive recombinant human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36 were prepubertal and 8 were in early puberty (testicular volume between 4 and 8 ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week by daily subcutaneous injection for 1-5 years. The year before rhGH therapy served as a control period. During the 1st year of treatment, mean growth velocity increased from 3.5 to 7.0 cm/year (P <0.0001) and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years (P <0.0001), but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity (P <0.0001), with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year. [ABSTRACT FROM AUTHOR]

The insulin and growth hormone responses to arginine and the growth hormone response to insulin were studied in 10 children undergoing chronic hemodialysis 1) under usual dietary prescription and 2) after 7 days of dietary manipulation (DM) decreasing mean carbohydrate intake from 48 to 36% and increasing lipid intake from 42 to 54% (percent of total energy) with the polyunsaturated/saturated fatty acids ratio being increased from 0.2 to 2. Mean fasting insulin and growth hormone were significantly decreased after DM: 10.3 ± 3 μunits/ml and 19.9 ± 3.5 ng/ml before and 4.3 ± 0.8 μunits/ml and 9.3 ± 2.4 ng/ml after DM. The mean arginine-induced insulin peak and the growth hormone peaks after arginine and insulin remained very high after DM. There was no decrease of mean plasma triglycerides: 214 ± 30 mg/dl before and 237 ± 26 mg/dl after DM. However, two children who had the greatest decrease in carbohydrate intake exhibited a decrease of triglycerides and of arginine-induced insulin secretion. The percent variation of insulin area after DM was significantly correlated with the percent variation of plasma triglycerides. [ABSTRACT FROM AUTHOR]