Vitamin D metabolite requirements in dialysed children receiving recombinant human growth hormone.

BACKGROUND: The aim of the study was to assess the requirement of active vitamin D in dialysed children during treatment with recombinant human growth hormone (rhGH). METHODS: Twenty-six children (aged 5-15 years) were treated with rhGH for 6 months. The serum concentration of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium and phosphorus were measured in two groups of patients studied in the years 1994-1995 (group I) and 1995-1998 (group II) respectively. Group I received a constant dose of alfacalcidol that was sufficient to keep PTH below 200 pg/ml before rhGH treatment began. The serum PTH level was checked every 3 months. Alfacalcidol was administered to group II according to serum PTH levels checked on a monthly basis. RESULTS: In group I the PTH level increased after 3 and 6 months of rhGH treatment from mean level 73+/-60; 155+/-156 and 344+/-249 pg/ml respectively; P<0.05. AP activity increased after 6 months of treatment from 206+/-99 to 325+/-124 U/l respectively; P<0.01. The calcium level decreased from baseline after 3 months of treatment from 2.36+/-0.21 to 2.17+/-0.12 mmol/l respectively; P<0.05. In group II AP activity increased after 3 and 6 months of treatment from 272+/-169 to 332+/-192 and 404. 9+/-219.8 U/l respectively; P<0.01. The mean level of phosphorus decreased after 6 months from 2.15+/-0.28 to 1.70+/-0.39 mmol/l respectively; P<0.01. In group II the mean dose of alfacalcidol increased by 60.9%. CONCLUSIONS: In children with end-stage renal failure, higher doses of vitamin D are needed during rhGH treatment. During rhGH treatment, frequent control of serum PTH level is necessary.     

Somatic and renal effects of growth hormone in rats with chronic renal failure

Recombinant human growth hormone (rhGH) has been widely used to improve growth in children with chronic renal failure (CRF). However, there has been great concern that GH may aggravate renal disease and hasten the progression to end-stage renal failure. We therefore investigated the effect of prolonged administration of rhGH at various doses on somatic growth and renal function and structure in rats with CRF, divided into four groups based on rhGH dose (vehicle, 0.4, 2.0, and 10.0 IU/day). rhGH was administered subcutaneously daily for 8 weeks. The mean growth was significantly greater in rats treated with high-dose rhGH (10.0 IU) than those treated with low-dose rhGH (P = 0.0089) or vehicle (P = 0.0011). Body weight gain increased in parallel with body length (Creatinine clearance at the end of the experiment was significantly lower in rats on high or medium-dose rhGH than those on low-dose rhGH and controls (P <0.05). The glomerular sclerosing index was greater in rats treated with higher doses of rhGH. There were significant differences between rats treated with high-dose rhGH and controls (P = 0.0144) and also between rats on medium-dose rhGH and controls (P = 0.0065). Although there was no significant difference, rats treated with higher doses of rhGH tended to excrete more protein. Renal insulin-like growth factor-I (IGF-I) content and circulating IGF-I and IGF-II levels did not significantly differ among groups. We conclude that: (1) GH improves somatic growth failure in rats with CRF, but prolonged administration of GH dose-dependently induces deterioration in renal function and structure and (2) this effect was induced neither via circulating IGF-I and IGF-II nor by local production of IGF-I, but seems to be direct. Received June 7, 1996; received in revised form and accepted November 19, 1996     

Effects of short-term recombinant human growth hormone therapy on plasma leptin concentrations in dialysis patients.

BACKGROUND: Hyperleptinaemia is a well-known biochemical feature found in uraemic patients. However, little is known about the hormonal regulation of leptin in chronic renal disease. Recent studies have shown that circulating leptin levels are modified by treatment with recombinant human growth hormone (rhGH), by recombinant insulin-like growth factor I (rhIGF I), or by a combination of rhIGF I plus rhGH in patients with chronic renal failure. We performed a prospective study to assess plasma leptin concentrations in a group of dialysis patients both before and during short-term rhGH therapy. METHODS: We studied eight dialysis patients (four haemodialysis (HD) and four on continuous ambulatory peritoneal dialysis (CAPD); three female, five male; mean age 63.9 +/- 3.1 years). All patients were instructed to maintain a stable diet (35 kcal/kg/day and 1 g protein/kg/day ideal body weight) and were treated with rhGH (0.2 IU/kg/day s.c.) for 4 weeks. Blood samples were taken at 0, 2, 4, and 8 weeks for determination of leptin, GH, and IGF I. Serum insulin concentrations were assessed at 0 and 4 weeks. RESULTS: Mean plasma leptin concentrations were elevated (36.2 +/- 12.8 ng/ml) at study outset and increased progressively throughout the 4 weeks of rhGH therapy (43.7 +/- 13.5 ng/ml (2 weeks, NS) and 70.6 +/- 18.4 ng/ml (4 weeks, P<0.0001)). These values returned to baseline levels (38.0 +/- 12.0 ng/ml, NS) at 1 month after rhGH withdrawal. rhGH therapy was accompanied by the development of direct correlations between leptin and IGF I concentrations at 2 weeks (r=0.86, P<0.01), and with correlations between leptin and IGF I (r=0.84, P<0.01) and between leptin and insulin (r=0.88, P<0.01) after 4 weeks of rhGH administration. CONCLUSION: These results confirm the presence of high circulating plasma leptin in dialysis patients and show that these levels are further increased by exogenous rhGH administration. The increase in plasma leptin after rhGH therapy may be related to the rhGH-induced changes in insulin in these patients.     

Influence of growth hormone and insulin-like growth factor-I on kidney function and kidney growth

Decreased glomerular filtration rate (GFR) in hypopituitarism and increased GFR in acromegaly suggest that growth hormone (GH) has a substantial effect on renal haemodynamics. Extractive and recombinant human (rh) GH in healthy volunteers increased effective renal plasma flow (ERPF) and GFR by 10% and 15% respectively. Renal response to GH was delayed and occurred at the same time as an increase in plasma insulin-like growth factor (IGF)-I values, whereas infusion of rhIGF-I promptly increased GFR and ERPF, indicating that the haemodynamic response of the kidney to GH is mediated by IGF-I. In chronic renal failure (CRF), the acute effect of GH on GFR is obliterated. This might protect the diseased kidney against the undesired consequences of hyperfiltration. Indeed, rhGH treatment for 1 year in children with CRF did not lead to an accelerated decline in GFR compared with the year before treatment. GH and IGF-I also effect renal growth. Exposure to excessive GH in transgenic mice causes renomegaly and progressive glomerular selerosis. In acromegalic humans, increased renal size and weight and increased glomerular diameter are well known, whereas renal failure is not a long-term hazard. At least in normal and hypophysectomized rats treated with doses comparable with the therapeutic regimens used in stunted children, rhGH increased renal weight but in proportion to the increase in body weight indicating an isometric effect of GH on renal growth. From these data, major renal longterm side effects of rhGH treatment in children with CRF appear unlikely.     

The effect of short-term growth hormone treatment on growth and energy expenditure in burned children.

Delays in growth are commonly observed in children who have sustained a severe cutaneous burn. The reasons for this growth delay are not completely known, but in adults, plasma growth hormone (GH) levels have been shown to decrease after thermal injury. If this is also the case in severely burned children, the low GH levels may contribute to their chronic growth delay. We propose that treatment with rhGH may prevent this burn-induced growth delay. Height velocities were measured for up to 2 years after injury in 38 burned children (age 7+/-1 years) with a 64+/-2% total burn surface area (TBSA) burn and a 59+/-3% third-degree burn who received 0.2 mg/kg/day rhGH during hospitalization. These height velocities were compared to 41 burned children (age 8+/-1 years) with a 64+/-3% TBSA burn and a 60+/-3% TBSA third-degree burn who were treated similarly but did not receive rhGH. Height velocities and height percentiles were compared to standard height velocity and percentile nomograms of unburned children. To determine the effect of rhGH on energy requirements, resting energy expenditures (REE) were measured by indirect calorimetry and compared to values calculated from the Harris-Benedict equation. All data are presented as mean+/-S.E.M. No differences in average height percentile could be shown between those receiving GH and controls at admission and 6 months after burn. There was, however, a significant difference (P<0.05) in height velocity during the first 2 years after burn between GH (47th+/-6 percentile) and controls (32nd+/-5 percentile). For rhGH-treated children, the REE was elevated by 34+/-4% versus 35+/-5% for controls. Recombinant human GH, given during acute hospitalization, maintained growth in severely burned children who would otherwise experience a significant growth delay. Treatment with rhGH did not atttenuate their elevated REE.     

Administration of ghrelin to young uraemic rats increases food intake transiently, stimulates growth hormone secretion and does not improve longitudinal growth.

BACKGROUND: Ghrelin administration stimulates appetite and growth hormone (GH) secretion. Whether these effects are preserved in young individuals with chronic renal failure (CRF) and their potential benefit on growth is questioned. METHODS: Three experiments were performed in subtotally nephrectomized young rats (Nx). (i) Food intake was monitored in CRF rats receiving saline intraperitoneally or a ghrelin dose (30 nmol) shown to increase food intake over 2 and 24 h in rats with normal renal function. (ii) Plasma levels of GH were measured after a dose of intravenous ghrelin (3 nmol) was given to three groups of five rats each: Nx, sham-operated fed ad libitum (SAL) and sham-operated pair-fed with Nx (SPF). (iii) Growth of Nx rats treated with intraperitoneal ghrelin (3 nmol) for 7 days (Nx-Ghr) was compared with that of SAL and Nx groups receiving saline (n=8-10 per group). RESULTS: In CRF rats, the dose of 30 nmol of ghrelin increased food consumption for 2 h (1.3+/-0.2 g vs 0.5+/-0.2 g, P<0.05) but not 24-h food intake (12.5+/-0.6 g vs 12.2+/-0.5 g). Ghrelin (3 nmol) increased plasma levels of GH, which were maximal 10 min after injection, no differences being observed among groups (SAL: 666.2+/-104.6 ng/ml; Nx: 691.6+/-90.7 ng/ml; SPF: 577.8+/-125.4 ng/ml). Return to basal GH levels was delayed in Nx. Ghrelin did not improve body length and weight gains, longitudinal bone growth rate or food intake in the Nx-Ghr group. CONCLUSIONS: In young uraemic rats, ghrelin increases appetite but not 24-h food intake, stimulates GH secretion and does not improve growth.     

重组人生长激素联合低热量营养支持对胃肠外科术后氮平衡和血糖的影响

目的观察重组人生长激素（rhGH）联合低热量营养对胃肠外科择期手术后患者的营养支持效果及对血糖的影响。方法将48例择期胃肠外科术后患者随机分为rhGH组和对照组，两组治疗和营养支持方案相同，rhGH组于术后第3-9天给予rhGH。在术前1d、术后3d和10d分别测定两组患者的体质量、血常规、肝肾功能和血浆蛋白指标，并每日检测氮平衡和血糖水平，观察并发症及不良反应，同时记录每日胰岛素用量。结果术后第10天，rhGH组累计氮平衡（13．21g）和血浆纤连蛋白水平[（104．77±19．94）mg/L]优于对照组[-6．88g和（93．03±16．03）mg/L]（P〈0．05）；术后第4天和第6-9天，rhGH组每日氮平衡均优于对照组（P〈0．05）；rhGH组治疗期间血糖水平升高[术后6d（7．68±2．15）mmol／L比（5．95±2．34）mmol／L，P〈0．05]，可为胰岛素有效控制，未发生严重并发症。结论rhGH联合低热量营养支持可以安全地促进蛋白合成和维持正氮平衡。改善营养状况和预后。     

Growth hormone secretion and sensitivity in men with idiopathic osteoporosis

Previous studies have suggested that insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) have a pathogenetic role in idiopathic osteoporosis. To investigate this question further we compared 20 men with idiopathic osteoporosis with 12 healthy, age-matched men regarding growth hormone (GH) secretion and sensitivity. GH samples were drawn every 30 minutes for 24 hours from 12 of the patients and all controls, and cumulated GH secretion (24hGH) was derived. Peak GH secretion (peakGH) was provoked by an insulin tolerance test. There were no differences between the groups in serum IGF-I (162 ± 30 vs 163 ± 47 μg/liter, mean ± SD), IGFBP-3 (2474 ± 263 vs 2568 ± 197 μg/liter), 24hGH (1.34 ± 1.26 vs 0.79 ± 0.43 U), or peakGH (53.0 ± 21.5 vs 44.1 ± 19.8 mU/liter). Patients and controls were given GH (2.4 U/day) for 1 week. Serum levels of markers for bone turnover increased significantly in both groups, with no difference in response to GH between the groups. The increase in urinary bone resorption markers was only significant in the controls. In the patients, but not in the controls, there were significant positive correlations between indices for GH secretion and markers for bone turnover at baseline and significant negative correlations with relative changes in bone markers during GH treatment. In this study no difference in GH secretion was found between men with idiopathic osteoporosis and controls, but the findings suggest that the GH/IGF-I axis could play a regulatory role in bone metabolism in men with this condition.     

Distrubance of growth hormone-insulin-like growth factor axis in uraemia

The growth hormone/insulin-like growth factor (IGF) axis is disturbed in uraemia. Elevated plasma growth hormone (GH) levels despite diminished growth suggest GH resistance, which may be due in part to a decreased expression of the growth hormone receptor at the cell membrane. The hepatic production of IGFs under the control of GH is impaired. Furthermore, there is an excess of IGF-binding protein over total IGF as a consequence of reduced renal clearance of low-molecular-weight subunits of the IGF-binding protein (IGF-BP). This results in an absolute (diminished production) and a relative (low bioavailability) deficiency of IGF. Recombinant human growth hormone (rhGH) in doses of 4 IU/m² per day is able to induce catch-up growth in children with preterminal and terminal renal failure. The growth stimulation of exogenous GH is attributed to its potency to increase the ratio of IGF-I to IGF-BP, followed by a normalization of IGF bioactivity. In renal transplanted children growth is not only disturbed by decreased renal function but also by steroid treatment. Corticosteroids, are responsible for catabolism, for suppression of pituitary GH secretion and for inhibition of local production of IGFs. Exogenous rhGH is able to counteract these growth-inhibiting effects. However, it remains to be seen whether long-term GH treatment definitely improves final adult height.     

Short-term recombinant human growth hormone therapy does not modify growth hormone, thyrotropin and prolactin responses to thyrotropin-releasing hormone in adult dialysis patients.

BACKGROUND: We recently have reported the first randomized, controlled study on the effects of short-term recombinant human growth hormone (rhGH|| therapy on the nutritional status of a group of malnourished adult dialysis patients. In order to evaluate whether rhGH administration exerts any influence on GH, thyrotropin (TSH|| and prolactin (PRL|| responses to TSH-releasing hormone (TRH||, we assessed these responses before and after rhGH therapy. METHODS: GH, PRL and TSH responses to TRH before and 1 month after rhGH therapy in a group of adult dialysis patients were evaluated. Seventeen dialysis patients (11 on continuous ambulatory peritoneal dialysis/six on haemodialysis|| were studied (rhGH group, n=8; control group, n=9||. In the rhGH group, 0.2 IU/kg/day rhGH was administered subcutaneously. Each patient was tested with TRH (400 microg bolus i.v.|| on two separate occasions, just before and immediately after the treatment period. RESULTS: rhGH treatment did not modify baseline serum GH concentrations (6.6+/-2.7 vs 4.1+/-1.1 microg/l||, paradoxical GH responses to TRH (six out of eight patients||, GH peak (11.9+/-4.6 vs 11.2+/-5.3 microg/l, NS|| or area under the secretory curve of GH (GH AUC; 19.1+/-4.5 vs 12.1+/-3.1 microg/h/l||. Both basal PRL (35.5+/-7.1 vs 36.7+/-8.6 microg/l|| and TSH (2.3+/-1.1 vs 2.8+/-1.7 mU/l|| concentrations, as well as their responses to TRH stimulation (PRL peak, 59.9+/-16.6 vs 59. 5+/-11.8 microg/l; TSH peak, 6.2+/-2.6 vs 7.1+/-3.9 mU/l||, were also unaffected by rhGH therapy. CONCLUSION: These results suggest that short-term rhGH therapy does not significantly influence the magnitude of the somatotropic, lactotropic or thyrotropic response to TRH in adult dialysis patients. However, this finding has to be interpreted with caution due to the two different patient groups included in this study.     

Plasma growth hormone-binding activity is low in uraemic children

Plasma growth hormone-binding protein (GH-BP) activity was evaluated in two groups of prepubertal children with chronic renal failure (CRF) who had been treated with recombinant human GH (rhGH). Group 1 consisted of eight children (mean chronological age 10.8 years) with advanced renal failure; group 2 consisted of nine children (mean chronological age 6 years) presenting with end-stage renal disease, who were on dialysis. Before treatment the specific binding of (¹²⁵I)hGH to highaffinity GH-BP was low in the two groups (group 1, 17.3±1.6% of radioactivity; group 2, 14.2±1.4%) compared with the mean value obtained in normal prepubertal children (24.8±1.7%). No significant changes in GH-BP activity were found during the 1st year of GH therapy, although growth velocity and plasma levels of insulin-like growth factor-I increased significantly in both groups. The low GH-binding activity found in children with CRF supports the state of GH resistance. The reason for the absence of a GH-BP response to GH therapy has to be clarified.     

Effects of growth hormone on kidney function in pediatric transplant recipients

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6±3.4 years) received rhGH daily (0.04–0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20±8 months) of rhGH treatment. Their mean serum creatinine level was 1.3±0.7 mg/dl 12 months before, and increased to 3.4±4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.06). Their mean calculated glomerular filtration rate was 58±20 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.     

Factors influencing the response to growth hormone in children with renal disease

The effects of age, height velocity over the preceding year, glomerular filtration rate (GFR) and prednisolone dose on growth response have been assessed by single and multiple linear regression analysis in 23 prepubertal children [age, mean (SD), 8.2 (2.5) years] with chronic renal failure (CRF) and 16 prepubertal children [12.1 (2.3) years] with renal transplants treated for 1 year with recombinant human growth hormone (rhGH), 30 U/m² per week. Height velocity [mean (SD), cm/year increased from 4.7 (1.3) to 9.7 (2.1) (P<0.0001) in the CRF group and 3.1 (1.6) to 7.3 (2.8) (P<0.0001) in the transplant group. In the CRF group, there was a correlation between age and height velocity, both in the pretreatment year (r=–0.755,P<0.0001) and during treatment (r=–0.421,P=0.045). There was no correlation between pretreatment height velocity or GFR and response to rhGH. In the transplanted children height velocity during the treatment year correlated with age (r=–0.647,P=0.007), prednisolone dose (r=–0.689,P=0.003), GFR (r=0.542,P=0.030) and pretreatment height velocity (r=0.655,P=0.006). Multiple regression analysis showed prednisolone dose and age to be the most important predictors of response.     

Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.     

Growth hormone/insulin-like growth factor system in children with chronic renal failure

Disturbances of the somatotropic hormone axis play an important pathogenic role in growth retardation and catabolism in children with chronic renal failure (CRF). The apparent discrepancy between normal or elevated growth hormone (GH) levels and diminished longitudinal growth in CRF has led to the concept of GH insensitivity, which is caused by multiple alterations in the distal components of the somatotropic hormone axis. Serum levels of IGF-I and IGF-II are normal in preterminal CRF, while in end-stage renal disease (ESRD) IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated GH levels in ESRD, these serum IGF-I levels appear inadequately low. Indeed, there is both clinical and experimental evidence for decreased hepatic production of IGF-I in CRF. This hepatic insensitivity to the action of GH may be partly the consequence of reduced GH receptor expression in liver tissue and partly a consequence of disturbed GH receptor signaling. The actions and metabolism of IGFs are modulated by specific high-affinity IGFBPs. CRF serum has an IGF-binding capacity that is increased by seven- to tenfold, leading to decreased IGF bioactivity of CRF serum despite normal total IGF levels. Serum levels of intact IGFBP-1, -2, -4, -6 and low molecular weight fragments of IGFBP-3 are elevated in CRF serum in relation to the degree of renal dysfunction, whereas serum levels of intact IGFBP-3 are normal. Levels of immunoreactive IGFBP-5 are not altered in CRF serum, but the majority of IGFBP-5 is fragmented. Decreased renal filtration and increased hepatic production of IGFBP-1 and -2 both contribute to high levels of serum IGFBP. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action in growth plate chondrocytes by competition with the type 1 IGF receptor for IGF binding. These data indicate that growth failure in CRF is mainly due to functional IGF deficiency. Combined therapy with rhGH and rhIGF-I is therefore a logical approach.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany     

Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9–13.9) years, GFR 19 (9–58) and ERPF 77 (34–271) ml/min per 1.73 m². During treatment height velocity increased from 4.5 (1.7–6.5) to 9.5 (4.8–12.7) cm/year (P<0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6–56) and after 1 year, 20 (9–59) ml/min per 1.73 m². ERPF increased to 96 (33–276) ml/min per 1.73 m² on day 8P=0.005), and remained elevated, but not significantly so, at 99 (24–428) ml/min per 1.73 m² at 1 year. Fasting IGF-I increased from 147 (46–315) ng/ml to 291 (61–673) by day 8P<0.003), and to 341 (101–786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment. The significance of increased ERPF after 1 week of rhGH in CRF is unclear, but long-term follow-up of renal function is indicated.     

Long-term recombinant human growth hormone use in Australian children with renal disease

BACKGROUND: Recombinant human growth hormone (rhGH) has been used for 15 years to treat Australian children with short stature caused by chronic kidney disease. The Australia-wide growth hormone database, OZGROW, has prospectively collected data for all patients treated with rhGH. The impact of rhGH therapy on linear growth in patients with chronic renal failure (CRF) was assessed by retrospectively analysing this data. METHODS: Growth data prior to and during treatment, bone age, and pubertal data were recorded from the database. Questionnaire data provided further information on underlying renal disease, medication use, bone disease, and final height. Patients were classified according to treatment modality; conservative management of CRF, haemodialysis or peritoneal dialysis, and transplant. RESULTS: Data on 183 patients were analysed. The duration of rhGH therapy ranged from 1.2 to 10.5 years (mean 5.3 years). The height standard deviation score (Ht SDS) in each patient group at the start and end of rhGH treatment were as follows: Predialysis: -2.6 to -2.1; dialysis: -2.7 to -2.3; transplant: -3.1 to -2.8 (P = 0.0001). Thirty-nine patients achieved final adult height, with mean Ht SDS before rhGH therapy being -2.65, and at final height it was 2.3. The mean final height for the males was 161.8 cm and for the females, it was 149.5 cm. CONCLUSION: The effect of treatment with rhGH was less dramatic than reported in the literature. However, the positive benefit of rhGH therapy was apparent both in the short and long-term. Therapy with rhGH maintained a steady Ht SDS with time; without rhGH, it would be anticipated that many children would show a steady decline in Ht SDS. The maximum benefit was seen in preterminal renal failure, and early therapy (before dialysis or transplantation) is recommended before an irrecoverable loss of height potential occurs.     

生长激素治疗对烧烫伤小儿生长发育的影响

目的：评价短期应用重组人生长激素（rhGH）对小儿烧烫伤的治疗效果及治疗后对其生长发育的影响。方法：选取82例住院烧烫伤患儿,随机分为rhGH治疗组58例和对照组24例。rhGH治疗组在常规治疗的基础上给予rhGH皮下注射0．3IU／kg,每晚1次,连续使用10d。对照组只给予常规治疗,于相应时间皮下注射2m1生理盐水。另选30例发育正常的整形患儿作为正常对照。动态观察应用rhGH（或生理盐水）前1d、应用后5d后,出院时及出院后6、12、18、24个月两组患儿血生长激素、血糖水平;患儿于入院时测量身高、体重,计算体质指数（BMI）,出院后6～24个月进行追踪性观察,与同时期同年龄段北京市正常小儿生长指标进行对比,评价影响。结果：rhGH治疗组创面愈合速度较对照组明显加快;创面愈合后瘢痕增生及痛痒程度明显轻于对照组,差异有显著性（P〈O．05）。rhGH治疗前两组血生长激素水平均明显低于正常水平。rhGH治疗第5天患儿的生长激素水平明显高于正常组水平和对照组（P〈0．001）,至出院时两组均趋于正常。伤后两组血糖水平均有轻度升高,激素治疗第5天恢复正常,但差异无显著性,两组之间各时间比较差异均无显著性。两组出院时体重和BMI均低于北京市儿童正常标准,但两组间身高、体重和BMI差异均无显著性。结论：临床短期小剂量使用生长激素治疗小儿烧烫伤能够加速创面愈合,提高创面愈合质量。创面愈合后小剂量短期应用的生长激素不会对小儿的生长发育造成后续影响。     

Serum bone GLA-protein in growth hormone deficient children

Serum bone GLA-protein (BGP), a sensitive and specific marker of bone formation, was measured in 54 normal children and in 50 children with growth disorders. In normal children, the pattern of variations of serum BGP with age was similar to the pattern of variations of the growth velocity. Mean serum BGP was very high during the first year of life (25.3 +/- 8.5 ng/ml), decreased to 14.8 +/- 2.2 ng/ml from 2 to 6 years, increased to 18.4 +/- 4.1 ng/ml from 7 to 10 years and to 18.8 +/- 6.5 ng/ml from 11 to 14 years. After puberty, mean sBGP decreased to 12.9 +/- 5.4 ng/ml from 15 to 18 years and to 6.5 +/- 1.4 ng/ml in young adults. In 32 patients with untreated growth hormone (GH) deficiency, mean sBGP was markedly lower than in age matched controls (6.8 +/- 4.4 ng/ml vs. 17.5 +/- 4.9 ng/ml, p less than .001). In 19 patients with GH deficiency who were undergoing treatment with human GH, sBGP was higher than in untreated patients (20.5 +/- 9.3 ng/ml vs. 6.8 +/- 4.4 ng/ml, p less than .001) and was not different from controls. Repeated measurements performed in 14 GH-deficient patients under chronic GH therapy showed that serum BGP: (1) increased in most patients during treatment (p less than .005); (2) was correlated with the duration of treatment (p less than .001); (3) decreased to pretreatment values after discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Homocysteine,folate, vitamin B<Subscript>12</Subscript> levels,and<Emphasis Type="Italic"> C677T</Emphasis> MTHFR mutation in children with renal failure

Hyperhomocysteinemia is well documented in chronic renal failure (CRF) and premature and progressive occlusive vascular disease is common in CRF. The combined effects of renal failure, folate and vitamin B(12) levels, and a common mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene that leads to total plasma homocysteine (tHcy) elevation in CRF children were investigated. Forty-two children (15 females) with CRF, mean age 10.3+/-4.7 years, were included. The mean glomerular filtration rate (GFR) was 37.3+/-16.9 ml/min per 1.73 m(2). The control group comprised 33 children (18 females) with a mean age of 8.6+/-3.4 years. There were 40% of CRF patients with hyperhomocysteinemia. Folate and vitamin B(12) deficiencies were identified in 14% (n=6) and 5% (n=2), respectively, of all patients. On univariate analysis, the tHcy serum concentration was negatively correlated with the plasma folate concentration (P<0.05) in controls, and with GFR (P<0.05) in patients. On multiple regression analysis for the predictors of tHcy serum concentrations, folic and vitamin B(12 )were significant in controls, whereas only GFR was significant in CRF children. In our patients no effect of the MTHFR polymorphism on tHcy levels was seen This result, in addition to the limited number of patients, may partially be explained by the low prevalence of folate deficiency in our patients.