Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation.

Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.

Blood pressure in schoolchildren measured under standardized conditions.

The blood pressures of 6346 children who were between the ages of seven and 17 years were measured under standardized conditions. Blood pressures were similar in prepubertal boys and girls. After puberty, the systolic blood pressures of the girls remained unchanged whereas those of the boys continued to rise. The difference between the fourth and fifth Korotkoff sounds was 2 mm at both the 50th and 95th percentiles. The systolic blood pressure was observed to fall over a 10-min period by 4-9 mmHg at the 50th percentile and 9-15 mmHg at the 95th percentile. Over the same period of time, the diastolic blood pressure was seen to fall by 2-3 mmHg and 3-6 mmHg at the 50th and 95th percentiles, respectively. There was no further fall in blood pressure after 10 min. The conditions and timing of measurement are important in blood-pressure evaluation and may explain the differences in blood pressure that have been reported for different populations.

Evaluation of long-term aggressive dietary management of chronic renal failure in children.

Ten children with chronic renal failure (CRF) were managed for 3 years using a strict low-protein and low-phosphorus diet supplemented by a mixture of the keto and amino forms of the essential amino acids and histidine (phase II). All of these children were previously managed for at least 2 years with a less rigorous diet of limited protein intake with no specific reduction of phosphorus (phase I). Energy, vitamin D, bicarbonate, phosphate binders and vitamin and mineral mixtures were added as required during both dietary phases. Data on dietary intake showed a significant fall in protein and phosphorus intake and a rise in calcium intake during phase II compared with phase I. Plasma calcium increased and phosphate fell, with an associated fall in intact parathyroid hormone levels. There was a marked improvement in urea creatinine ratios, which suggested an improved anabolic state. Cholesterol and triglyceride levels were improved. Height and weight velocity were increased, becoming significant after 3 years of phase II. Renal function deteriorated at a slower rate than predicted. The diet was well tolerated by the children, with fitness and school performance showing improvement. We conclude that long-term strict dietary management of children with CRF is feasible. Our data suggest an overall improvement in general health and an apparent reduction in the rate of deterioration of renal function.

Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone.

In a 12-month study, nine boys, aged 4.8-15.6 years, with bone ages 4.6-13 years, with moderate to severe chronic renal failure and resultant growth failure were treated with daily recombinant human growth hormone (rhGH), in conjunction with a strict low-protein/low-phosphate diet supplemented with keto and amino forms of the essential amino acids, histidine and additional energy. Improved growth had previously been observed with this dietary management over that obtained with conventional treatment for chronic renal failure. Each child had been on this diet for at least 2 years before rhGH was commenced. Mean height velocity increased from 4.6 +/- 1.3 to 9.0 +/- 1.3 cm/year (P < 0.001) in the pre-pubertal group, and in the pubertal group from 5.4 +/- 1.4 to 10.4 +/- 1.8 cm/year (P < 0.01). The mean height velocity standard deviation scores (SDSs) increased from -1.2 +/- 0.6 to +2.3 +/- 0.9 (P < 0.001) in the pre-pubertal group and from -0.4 +/- 0.6 to +1.9 +/- 1.1 (P < 0.01) in the pubertal group. Mean height SDS for chronological age increased from -2.2 +/- 0.7 to -1.5 +/- 0.5 (P < 0.01) in the pre-pubertal group and from -1.9 +/- 0.7 to -1.3 +/- 0.9 in the pubertal group (P < 0.02). There was no significant deterioration in renal function or renal bone disease, and bone age did not advance more than chronological age over the 12-month period.