Growth hormone for children with chronic renal failure and on dialysis

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean±SD duration of therapy 3.7±2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24±12 mL min^–1/1.73 m² at the start of rhGH. Their height standard deviation score improved from –2.5±1.4 to –2.1±0.7 at 1 year (P=0.3), –2.0±0.7 at 2 years (P=0.01), and –1.6±0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from –2.7±0.5 to –2.3±0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean±SD age of 12.1±4.0 years. Mean Ht SDS was –1.8±0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.     

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.     

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.     

Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS

We evaluated the utilization and potential benefits of recombinant human growth hormone (rhGH) in children with chronic kidney disease (CKD) and following renal transplantation in a large patient cohort. We queried the chronic renal insufficiency (CRI), dialysis, and transplant registries of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) to characterize the frequency of rhGH utilization, factors related to its usage, and the relationship between rhGH usage and catch-up growth. Data from 6,505, 5,122, and 4,478 CRI, dialysis, and transplant patients, respectively, was evaluated. Percentage utilization of rhGH 2 years after registry entry was 22%, 33%, and 3% in children with a height standard deviation score (SDS) <−1 and age <17 years (termed candidate group) in CRI, dialysis, and transplant patients, respectively. Multivariate logistic regression analysis showed that the likelihood of using rhGH was significantly correlated with age, gender, geographical region of residence and height category within the candidate group (p < 0.01). The use of rhGH was associated with catch-up growth in 27%, 11%, and 25% of candidate CRI, dialysis, and transplant patients, respectively. In the candidate group, percentage catch-up growth was highest in children who were Tanner stage 1–2, who comprised 19.4%, 7.1%, and 25.5% of the CRI, dialysis, and transplant patients, respectively. Using multiple regression analysis, the estimated impact of rhGH on final adult height (age >19 years) was 0.80, 0.50, and 0.19 SDS, in CRI, dialysis, and transplant patients, respectively. Thus, rhGH can improve height gain in some children with CKD. The use of rhGH appears to be most effective in prepubertal children with CRI.     

Short dialyzed children respond less to growth hormone than patients prior to dialysis

Recombinant human growth hormone (rhGH) is a new treatment modality for short children with chronic renal failure (CRF) prior to and during dialysis. It is difficult to analyze whether dialysis patients respond less to rhGH than children with CRF on conservative treatment because they are older and often in a pubertal age range. One hundred and eight patients were treated with 28–30 IU rhGH/kg per week for at least 1 year. We analyzed the growth response to rhGH in 56 prepubertal patients aged less than 10 years at the start of rhGH treatment; 38 children with a mean age of 6.5±2.4 years were on conservative treatment (CT) and 18 patients with a mean age of 6.5±2 years on dialysis treatment (D). Mean height velocity was 4.9±2.3 cm/year in children on CT and 4.6±1.8 cm/year in children on D. During the 1 st treatment year, height velocity was 9.5±3.8 cm/year in CT patients and 7.3±1.3 cm/year in D patients (P<0.05). The change in height was +1.1±0.8 standard deviation (SD) in CT patients and +0.5±0.4 SD in D patients (P<0.005). During the 2nd treatment year, the change in height was again greater in CT patients (0.5±0.4 SD vs. 0.2±0.4 SD;P<0.05). The difference in height velocity and change in height standard deviation score was also significant when a subgroup of patients was matched for sex, age, height. Height velocity and the change in height velocity during rhGH treatment were not correlated with residual renal function, the degree of anemia, or metabolic acidosis. We conclude that short children on D respond less to rhGH than short children on CT, indicating a greater insensitivity to rhGH during D treatment.Study group members: K. Bittner (Ansbach), J. H. H. Ehrich, G. Filler, J. Gellermann (Berlin), H. Hampel (Berlin), H. Bachmann (Bremen), H. Ruder (Erlangen), K. E. Bonzel, B. Scheller (Essen), J. Dippel (Frankfurt), L. B. Zimmerhackl (Freiburg), J. Kreuder, W. Rascher (Gießen), D. Müller-Wiefel (Hamburg), D. Haffner, O. Mehls, R. Nissel, E. Wühl (Heidelberg (coordinators)), J. Misselwitz, B. Rönnefarth (Jena), U. Querfeld (Köln), H. Eichstädt, C. Greiner, E. Keller (Leipzig), H. P. Weber (Lüdenscheid), H. R. Heise, D. Wiemann (Magdeburg), R. Beetz (Mainz), D. Sasse, M. Soergel (Marburg), K. Pistor, A. Zlotkowski (Moers), B. Klare (München), R. Eife (München), E. Kuwertz-Bröking (Münster), M. Wigger, M. Mix (Rostock), O. Eichler (Suhl)     

Long-term use of recombinant human growth hormone in pediatric allograft recipients: a report of the NAPRTCS Transplant Registry

Data from the NAPRTCS database were analyzed for growth, allograft function, and targeted adverse events (AE) over a 5-year period in 513 recipients who received recombinant human growth hormone (rhGH) treatment and compared with the outcome of 2,263 concurrent controls who did not receive rhGH. Recipients less than 10 years of age grew better than older recipients. Final adult height was superior in the rhGH-treated group compared with the control group. Allograft function and graft failure rate was similar in the rhGH-treated and control groups. No increased incidence of AE was noted in the rhGH-treated group. rhGH is effective and safe for use in growth-retarded pediatric renal allograft recipients.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     

Recombinant human growth hormone treatment of children following renal transplantation

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6–30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5±2.1 vs 5.7±2.7;P<0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potiental adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P<0.009) and 12 months (P<0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.     

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.     

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.     

Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (±SD) rhGH treatment observation period was 19.9±5.9 months. The mean age at the start of rhGH treatment was 8.3±3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43–2.66] than in prepubertal patients (1.19, 95% CI 1.01–1.40). Increases in PTH levels were significantly different between the two groups (=1.64, 95% CI 1.16–3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.     

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.     

The effect of rhGH on height velocity and BMI in children with CKD: a report of the NAPRTCS registry

The aim of this investigation was to evaluate the impact of recombinant human growth hormone (rhGH) therapy on height velocity (HV), estimated glomerular filtration rate (eGFR) and body mass index (BMI) in a large cohort of children with chronic kidney disease (CKD). We reviewed longitudinal data from patients enrolled in the chronic renal insufficiency registry of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Of the 7189 patients enrolled in the registry, 827 (11.5%) received rhGH. A total of 787 children with CKD previously rhGH naïve who received rhGH for 1–4 years (median 1.5 years) were paired with 787 control patients, and over 100 of the case–controls were followed for 4 years. The control group was matched for age, gender, height and length of time in the NAPRTCS registry. Height velocity was also compared to the general U.S. population. The eGFR of the treated group (37.5 ml/min per 1.73 m²) was significantly less than that of the control group (42.3 ml/min per 1.73 m²; p?p?p?p?相似文献   

The effect of recombinant human growth hormone treatment on bone and mineral metabolism in haemodialysis patients

Background: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism. Methods: Twenty chronic malnourished patients on haemodialysis took part in a double-blind, placebo controlled trial with subcutaneous injections of rhGH (4 IU/m²/day) or placebo for 6 months. Results: During rhGH treatment, serum IGF-1 increased 264±52% (mean±SEM) (P<0.008). There were no significant changes in biochemical markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid hormone). Among markers of bone metabolism, there was a significant increase in serum procollagen type I C-terminal propeptide (maximum 155±8%, P<0.001) and no significant changes in serum alkaline phosphatase. Bone densitometry showed a significant decrease in whole body bone mineral content (95.7±1.2%) after 6 months treatment. Conclusion: The effects of 6 months treatment with rhGH seen in this study are best explained by a GH- or IGF-1-induced increased bone turnover. Long-term treatment in larger cohorts followed by bone densitometry and, preferentially, bone histomorphometry are needed to evaluate whether this is a beneficial effect in haemodialysis patients.     

Effects of growth hormone administration in pediatric renal allograft recipients

The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2±2.0 years) all of whom had bone ages less than or equal to 12 years (10.0±1.4 years), a height standard deviation score of less than –2.5 (–4.9±1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40ml/min per 1.73 m² (51±6.8 ml/min per 1.73 m²), and stable renal function on alternate-day prednisone (16.7±2.6 mg/m² per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5±1.6 cm/year pre therapy, 8.5±1.4 cm/year post therapy,P<0.001) and percentage of expected growth velocity for bone age (67±31% pre therapy, 163±27% post therapy,P<0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH. The potential risk of deterioration in renal function due to rGH-induced hyperfiltration must be investigated.     

Recombinant human growth hormone treatment of children on hemodialysis

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. Received April 18, 1997; received in revised form October 23, 1997; accepted October 28, 1997     

Effects of growth hormone in short children after renal transplantation

From 1991 to 1993, 90 children having received a kidney graft with a post-transplantation period of at least 12 months were included in a prospective study carried out in 18 French pediatric centers. After informed consent and randomization, children received recombinant human growth hormone (rhGH) (Genotonorm, Pharmacia peptide hormones) 30 U/m² per week, either immediately on enrollment, for the treated group, or after 1 year of follow-up for the group serving as a control. After 1 year both groups were treated and we analyzed data during the subsequent years. Eighty-five children completed the 1-year study. Growth velocity was significantly increased by rhGH: 7.7 cm with a gain of +0.3 standard deviation score in the treated group versus 4.6 cm in the control group (P<0.0001) during the 1st year. Four factors predicted response to therapy: growth velocity prior to GH therapy, glomerular filtration rate (GFR) at the start, mode of corticosteroid administration, and degree of insulin resistance. After 1 year we observed a moderate, significant decrease in GFR in both groups. Biopsy-proven acute rejection episodes were not significantly more frequent during the 1st year in the group of patients who received rhGH: 9 in 44 versus 4 in 46 patients. The patients who rejected did not differ in terms of age, renal function at the start, and type of immunosuppression, but history of rejection before GH treatment was discriminatory: 6 of 17 children with two or more episodes had a new rejection versus 1 of 22 who had no or only one episode (P=0.01). Glucose tolerance was not modified after 1 year of GH therapy. During the subsequent years of treatment a decrease in growth velocity was noted: 5.9 cm at 2 years, 5.5 at 3 years, and 5.2 cm at 4 years. In conclusion, GH is efficient for improving growth velocity in short transplanted children, inducing clear-cut but limited catch-up growth. The risk of rejection was shown only in patients with a prior history of more than one rejection episode. Received October 3, 1997; received in revised form and accepted January 26, 1998     

Optimising nutrition in chronic renal insufficiency—growth

The need to optimise nutrition to promote growth in infants with chronic renal insufficiency (CRI) is well recognised, but there is less enthusiasm for such an approach in older children and those with milder degrees of CRI. Energy intakes and growth outcomes were prospectively monitored over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/ dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n=19) CRI. Children were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI), and were excluded if they required dialysis. None received growth hormone. Regular dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly anthropometric measurements were obtained. Mean height standard deviation score (SDS) was maintained in those with mild and moderate CRI and significantly increased in children with severe CRI [0.1 SDS (0.32 SD), F =9.45, 1 df, P =0.003]. There was a non-significant reduction in energy intake from dietary records overall (median –8.5% estimated average requirement), associated with poor adherence to supplements in severe CRI and under-reporting in the mild group. An increase in height or body mass index SDS, however, was observed in all children who took the supplements as prescribed. A correlation between change in energy intake and change in height SDS was observed in severe CRI ( r ²=0.58, P =0.011). Regular dietetic advice, with particular attention to adherence to optimise energy intake, may improve growth, irrespective of age and should form an integral part of the clinical care package.     

First-year response to rhGH therapy in children with CKD: a National Cooperative Growth Study Report

A clear definition of the appropriate growth response during recombinant human growth hormone (rhGH) treatment has never been established in the pediatric chronic kidney disease (CKD) population. We present here data from Genentech’s National Cooperative Growth Study (NCGS) on the first-year growth response in prepubertal children with CKD. Using NCGS data, we constructed response curves for the first year of rhGH therapy in 270 (186 males, 84 females) naïve-to-treatment, prepubertal children with CKD prior to transplant or dialysis. Data from both genders were combined because gender was not significantly related to height velocity (p?=?0.51). Response to rhGH was expressed as height velocity (HV) in cm/year. Mean, mean ± 1SD, and mean ? 2SD for HV during the first year of rhGH treatment as well as pretreatment HV were plotted versus age. Age-specific HV plots for rhGH-treated children with CKD are presented. At all ages, the first-year mean HV was greater than the mean pretreatment HV. The mean ? 2SD for HV in children on rhGH treatment was similar to the mean pretreatment HV. These growth plots will be useful to clinicians for assessing a patient’s first-year growth response. We propose that a HV below the mean ? 1SD is an inadequate response. These curves may help identify patients with a suboptimal growth response due to confounding medical factors and/or non-compliance.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

唑来膦酸对骨质疏松性股骨转子间骨折作用效果分析

 目的 比较应用唑来膦酸与降钙素对老年骨质疏松性股骨转子间骨折疗效的影响。方法 回顾性分析 2009年6月到2012年11月,采用闭合复位髓内钉固定术治疗610例骨质疏松性转子间骨折患者资料,按照入院顺序及是否获得完整随访资料将543例患者分为两组。其中降钙素组325例,2009年6月至2011年4月手术,男107例,女218例; 年龄(75.02±5.65)岁;Evans?Jensen分型：Ⅰ型87例,Ⅱ型136例,Ⅲ型102例;腰椎骨密度平均(0.737±0.08) g/cm²,髋部平均 (0.725±0.05)g/cm²;应用降钙素等治疗。唑来膦酸组218例,2011年5月至2012年11月手术,男82例,女136例; 年龄(74.71±5.32)岁;Evans?Jensen分型：Ⅰ型62例,Ⅱ型91例,Ⅲ型65例;腰椎骨密度平均为(0.738±0.05)g/cm²,髋部平均为(0.722±0.06)g/cm²;术后7d内使用唑来膦酸治疗。两组患者分别比较住院期间及术后1年骨密度值。采用Harris评分、视觉模拟评分(visual analogue score, VAS)评价髋关节功能和疼痛程度。结果 降钙素组随访时间为5～22个月,平均 12.8个月;唑来膦酸组随访时间为4～19个月,平均12.5个月。患者影像学骨折愈合时间、Harris评分、VAS评分,唑来膦酸组分别为(14.25±1.38)周、(68.88±5.71)分、(0.36±0.55)分;降钙素组分别为(14.39±1.12)周、(69.47±4.60)分、(0.33± 0.48)分;两组各指标比较,差异无统计学意义。术后1年唑来膦酸组腰椎骨密度平均为(0.76±0.06)g/cm²,髋部平均为 (0.75±0.04)g/cm²,降钙素组腰椎骨密度平均为(0.75±0.07)g/cm²,髋部平均为(0.74±0.07) g/cm²。唑来膦酸组患者术后1 年与术前骨密度比较差异有统计学意义。术后1年,两组骨密度比较,差异有统计学意义。结论 老年骨质疏松性股骨 转子间骨折内固定术后应用唑来膦酸未对骨折愈合和髋关节功能恢复造成影响,术后1年骨密度明显升高。