Predictors of final adult height after renal transplantation during childhood: a single-center study

AIM: Assessment of final adult height and its predictive factors in children transplanted (RTx) and followed up in a single center. METHODS: A cohort of 32 patients (17 boys, 15 girls) who received RTx before the age of 15 years and had reached a final adult height was selected. Twenty patients received a single RTx, 9 patients received two RTx, and 3 patients received three RTx. Seven children were transplanted preemptively, while the remaining 25 children received peritoneal dialysis for relatively short periods of time. In 11 patients, recombinant human growth hormone (rhGH) was administered either before (n = 8) or after (n = 3) RTx. RESUTLS: In 13 patiens (41%), the final height standard deviation score for chronological age (hSDS) was -2.3+/-0.5, below the 95% confidence limits for target height (group A), while in 19 patients (59%), it was -0.7+/-0.8, within the 95% confidence limits for target height (group B). The hSDS values at the start of dialysis and at the time of first RTx were significantly lower in group A than in group B. A higher hSDS at the start of dialysis and at the time of first RTx had a significant positive influence on the final height (FH), whereas a longer duration of dialysis had a significant negative effect on the FH. Administration of rhGH after RTx played an important role in the achievement of a normal FH in 3 girls. No differences were observed between group A and B with respect to age at start of dialysis, chronological or bone age at first RTx, number of rejection episodes, duration of the study period from last RTx to FH, glomerular filtration rate during this study period, or percentage of time on prednisone therapy. CONCLUSIONS: The FH is almost exclusively predetermined by the height achieved at the start of dialysis and at the time of first RTx. Therefore, to reach target adult height after RTx, the best strategy is to shorten the time of dialysis and to start rhGH administration at a young age and as early as possible during the course of chronic renal failure. Administration of rhGH after RTx is also highly effective, but, given its potential danger, still remains a matter of investigation.     

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.     

Height outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Objective:To retrospectively investigate the height outcome of patients with congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency(21-OHD).Methods:The 135 CAH patients with 21-OHD diagnosed in our hospital from Jan 1980 to Oct 2006 were retrospectively analyzed.The investigated parameters included final height(FH),FH standard deviation score(FH SDS),target height SDS(TH SDS),difference between TH and FH(TH-FH),FH SDS-TH SDS,the age of onset of sexual development,and the difference between bone age and chronological age(BA-CA)when patients got the FH.Results:Among the 135 patients,female/male=108/27.Mean FH was(156.8±5.4)cm(n=14)and(150.8±6.8)cm(n=76)for males and females,respectively.Mean FH SDS was(-0.6±0.8)(n=13)and(0.2±1.2)(n=54)for males and females,respectively.Sexual development began at(5.2±1.7)years old(y/o)(n=13)and(7.9±3.2)y/o(n=43)in males and females,respectively.Conclusions:The FH of CAH patients with 21-OHD was lower than that of the normal range.Effect of the disease on the height growth in male patients was more severe than that in females.All patients began sexual development much earlier than the normal age-matched group.Male patients began their sexual development even earlier.     

Post graft development of short children treated with growth hormone before kidney graft

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6±1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3.5±1.4 years. During treatment, mean height increased from –3.0±0.9 standard deviation score (SDS) to –1.9±1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1.2±0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5±0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: –0.5±0.4 SDS in patients grafted at early stages of puberty (P2–P3) and –0.15±0.9 SDS in patients grafted at late stages of puberty (P4–P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children. Received: 23 July 1998 / Revised: 8 December 1998 / Accepted: 13 December 1998     

Effect of renal transplantation in childhood on longitudinal growth and adult height

BACKGROUND: Severe growth failure is frequently observed in children suffering from end-stage renal disease (ESRD). METHODS: We analyzed the effect of renal transplantation (RTx) on longitudinal growth and final height in 37 children (19 girls) with ESRD with a mean follow-up of 8.5 years. The mean age at RTx was 11.3 years. RESULTS: In children transplanted before start of puberty, mean height velocity increased significantly from 4.9 to 8.0 cm/year (P < 0.01), resulting in an increase in standardized height of 0.6 SD within two years post RTx. Although peak height velocity during puberty was significantly increased compared with healthy children, total pubertal height gain was reduced by 20% because of its shortened duration. Mean standardized height significantly increased from the time of RTx until final height by 1.3 SD and 0.7 SD in children transplanted before and after start of puberty, respectively. Mean adult height (boys 170 cm; girls 151 cm) was normal (> -2 SD) in 68% of patients. Change in standardized height from RTx until adult height was associated with initial degree of stunting and glomerular filtration rate (GFR; cumulative r2 0.49). Total pubertal height gain was associated with the age at start of puberty, GFR, and age at RTx (cumulative r2 0.57). CONCLUSION: RTx in children with ESRD induces moderate catch-up growth during the prepubertal growth period. However, final height is reduced in about one third of patients due to the reduced pubertal height gain and preexisting height deficit at the time of RTx.     

The influence of G-protein beta3-subunit gene and endothelial nitric oxide synthase gene in exon 7 polymorphisms on progression of autosomal dominant polycystic kidney disease

BACKGROUND: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. We examined the influence of G-protein beta3-subunit C825T polymorphism and endothelial nitric oxide synthase Glu298Asp polymorphism on the progression of ADPKD towards end stage renal failure (ESRF). METHODS: 306 ADPKD patients (pts) were analyzed; 261 pts (136 males, 125 females) with ESRF, with subgroup of 73 pts (44 males, 29 females) with ESRF before 45 years (rapid progressors), 46 pts (20 males, 26 females) with ESRF later than in 63 years (slow progressors) and 45 ADPKD pts (17 males, 28 females) in mean age 51 years with serum creatinine under 110 micromol/L (slow progressors) and 100 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for G-protein beta3-subunit C825T genotype in exon 10 and for endothelial nitric oxide synthase Glu298Asp genotype in exon 7. RESULTS: The G-protein beta3-subunit C825T genotype exhibited no significant differences among the groups of slow progressors (6.6% (6/91) TT, 54.9% (50/91) CT, 38.8% (35/91) CC), rapid progressors (9.6% (7/73) TT, 46.6% (34/73) CT, 43.8% (32/73) CC), ADPKD group with ESRF between 40-63 years (9.2% (13/142) TT, 50% (71/142) CT, 40.8% (58/142) CC) and control group (12% TT, 44% CT, 44% CC). When comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages: males TT--51.7+/-8.8 years, CT--51.9+/-10.3 years, CC--49.7+/-10.2 years and females TT--56+/-9.9 years, CT--53.2+/-8.5 years, CC--53.9+/-8.7 years. The endothelial nitric oxide synthase Glu298Asp and Asp29Asp genotypes were significantly more frequent in rapid progressors (9.6% (7/73) Asp/Asp, 39.7% (29/73) Asp/Glu, 50.7% (37/73) Glu/Glu) and in ADPKD group with ESRF between 40-63 years (11.3% (16/142) Asp/Asp, 41.5% (59/142) Asp/Glu, 47.2% (67/142) Glu/Glu) in comparison with slow progressors (8.8% (8/91) Asp/Asp, 24.2% (22/91) Asp/Glu, 67.0% (61/91) Glu/Glu) and with control group (8% Asp/Asp, 32% Asp/Glu, 60% Glu/Glu) (Chi-square test, p<0.05). Comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages in males with Asp/Asp--54.9+/-10.4 years, Asp/Glu--50.2+/-9.4 years, Glu/Glu--51.0+/-10.4 years. We found out in homozygous Asp/Asp females significantly earlier onset of ESRF (49.2+/-5.6 years) in comparison with heterozygous females (53.3+/-7.2 years) and with Glu/Glu homozygous females (54.8+/-9.7 years) (t-test, p<0.05). CONCLUSION: We excluded the significance of G-protein beta3-subunit C825T polymorphism on the progression of ADPKD. We established the negative prognostic value of the carriers of Asp variant of eNOS polymorphism. Finding of new modifiers could have in future clinical consequences for ADPKD patients.     

Growth over 10 years following a 1-year trial of growth hormone therapy

The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0–10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5–14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1–18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from –2.9 (–3.7 to –2.2) to –1.9 (–2.9 to –0.5) over 4.0 (0.3–9.1) years of rhGH (P=0.04), and was –1.6 (–2.9 to –0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from –3.3 (–4.5 to –1.9) to –2.9 (–5.4 to –0.5) over 2.7 (1.0–6.0) years and was –3.0 (–6.3 to –0.1) at final height (NS). In group 3 Ht SDS increased from –3.4 (–4.3 to –2.6) to –3.0 (–3.4 to –2.2) over 1.4 (0.2–2.3) years (NS) and was –2.5 (–3.0 to –1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from –3.2 (–4.3 to –1.9) to –2.6 (–3.9 to –0.5) on rhGH (P=0.004) and to –2.2 (–4.4 to –0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment. Received: 18 November 1998 / Revised: 10 August 1999 / Accepted: 13 August 1999     

Head circumference in chronic renal failure from birth.

AIMS: Chronic renal failure in childhood jeopardizes both growth and development. In children with chronic renal failure from birth, growth in height and weight have been found to be generally poor. Few data on head circumference are available. MATERIAL: A cohort of 19 children with chronic renal failure from birth was studied from the early weeks of life to the age of 5 years. There were 18 boys; and 18 patients had congenital renal hypoplasia or hypodysplasia associated with obstructive uropathies. Eight patients received recombinant growth hormone (rhGH) after the age of 2 years. Only 2 patients needed renal replacement therapy before the age of 5 years. Data after transplantation were not included. METHODS: The following variables were analyzed: body height, body mass index and head circumference. Data were expressed in median values of standard deviations scores (SDS). RESULTS: In the first 3 months of life there was a significant drop in height SDS, body mass index SDS and head circumference SDS. Thereafter, a stable growth velocity was observed for the rest of the study period, except for body mass index SDS. which improved after 36 months. There was a striking difference between patients who needed treatment or not with recombinant human growth hormone (rhGH). Patients without rhGH displayed a stable growth after the age of 3 months until 5 years of age. In the remaining 8 patients, rhGH treatment resulted in a significant increase not only in height SDS but also in head circumference SDS. CONCLUSIONS: In infants and young children with chronic renal failure from birth, growth in head circumference parallels growth in body height. This applies to all patients and to data before and during rhGH treatment.     

Growth in adolescent hemodialysis patients: Data from the Centers for Medicare & Medicaid Services ESRD Clinical Performance Measures Project

The Centers for Medicare & Medicaid Services' (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project has collected data on all adolescent hemodialysis patients since 2000. Thus, by 2002 data were available on all adolescents on hemodialysis in the USA for 3 consecutive years. Possible associations between clinical parameters and linear growth in this cohort were evaluated. Ninety-four adolescents were on hemodialysis for the 3 study years. The mean height standard deviation score (ht SDS) fell from -1.97 to -2.36 over the 3 study years. Compared with patients with ht SDS > or =-1.88, patients with ht SDS <-1.88 in the 2002 study year (n =53) were more likely to be male (66% vs 44%, p <0.05), on dialysis longer (6.9+/-4.5 years vs 4.1+/-2.3 years, p <0.001), and had lower height SDS in the 2000 study year (-2.90+/-1.31 vs -0.772+/-1.10, p <0.001). Patients with a ht SDS <-1.88 had a lower mean hemoglobin (11.4+/-1.6 g/dl vs 12.0+/-1.1 g/dl, p <0.05), but there were no differences in other clinical parameters. Among patients with ht SDS <-1.88, 38.8% (n =20) were prescribed recombinant human growth hormone (rhGH) in the 2002 study year. There were no differences in demographic or clinical parameters between rhGH treated and untreated patients. Many adolescents who remain on hemodialysis have poor linear growth. Further evaluation is needed to delineate contributory factors and the possible underutilization of rhGH.     

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.     

Results of recombinant growth hormone treatment in children with end-stage renal disease on regular hemodialysis

Children with chronic kidney disease are at high risk for growth retardation and decreased adult height. Growth hormone (GH) treatment is known to stimulate growth in children with short stature suffering from chronic kidney disease. However, the extent to which this therapy affects final adult height is not known. This study was performed on 15 patients with end-stage renal disease (ESRD) on regular hemodialysis to detect the effect of using recombinant human growth hormone (rhGH) on growth of patients with ESRD on regular hemodialysis and comparing this effect with the growth velocity in the same group without using rhGH in the year before therapy. There were eight females and seven males with mean age 10.6 ± 2.8 (range 5-14 years). For each patient, recombinant GH was given for one year, three-times weekly. The data of these 15 patients was compared with the year before treatment versus data of the same group of patients after six months and after one year of rhGH therapy. Our results showed that, in the year before therapy, height of these patients increased from a mean of 112.1 ± 11.6 cm to 112.7 ± 11.5 cm, which is a non-significant increase statistically (P >0.05) as well as clinically (mean growth velocity 0.6 cm/year), while height of these patients increased from a mean of 112.7 ± 11.5 cm at the start of therapy to 116.8 ± 11 cm after therapy for one year, which, although statically not significant (P >0.05), was of clinical significance as it makes rate of increase, i.e. the mean growth velocity, 4.1 cm/year close to the normal growth velocity, which is 5 cm/year, before puberty. rhGH therapy for patients with ESRD on regular hemodialysis is helpful in height gain and catch-up growth even when given three-times per week instead of five- or six-times per week. We recommend giving rhGH therapy as a routine supplementation to pediatric patients before epiphyseal closure.     

Plasma levels of soluble CD30 are increased in children with chronic renal failure and with primary growth deficiency and decrease during treatment with recombination human growth hormone.

BACKGROUND: Previous studies have suggested that in vivo Th2 lymphocyte activation is related to increased soluble CD30 (sCD30) plasma levels. As various hormones (dehydroepiandrosterone, glucocorticoids, progesterone) can regulate the Th1/Th2 balance, and because growth hormone (GH) enhances lymphocyte function, we measured sCD30 plasma levels, before and after treatment with recombinant human GH (rhGH), in children with growth failure due to chronic renal failure (CRF) or to isolated GH deficiency in order to evaluate the potential effects of rhGH treatment on Th1/Th2 balance. METHODS: sCD30 plasma levels were determined by ELISA assay in 30 children with CRF (mean age 10.7+/-3.7 years), in five children with isolated GH deficiency (mean age 11.4+/-2.6 years), and in 10 normal controls (mean age 10.1+/-3.5 years). RESULTS: sCD30 levels were higher in the 30 children with CRF than in the 10 controls (179.8+/-79.4 vs 11.3+/-10.9 U/ml, P<0.001) exhibiting an inverse correlation with glomerular filtration rate (GFR) (r=-0.7860, P<0.001). In 11 children with CRF, after 19.9+/-16.7 months of rhGH treatment, a decrease of sCD30 plasma level (170+/-50 vs 134+/-49 U/ml, P<0.01) was observed. The five children with primary GH deficiency had higher sCD30 plasma level than controls (mean 147+/-105 vs 11+/-10 U/ml, P<0.004) and sCD30 plasma levels decreased to 95.2+/-109.6 U/ml after rhGH treatment. CONCLUSIONS: The finding that rhGH treatment decreased sCD30 plasma levels in children with CRF, and that children with primary GH deficiency had higher sCD30 plasma levels than controls, suggest that GH may regulate CD30 expression and possibly the balance of Th1/Th2. Whether the uraemia-induced increase in sCD30 is due to decreased renal excretion, to overproduction or both, remains to be determined.     

Short stature and growth hormone use in pediatric hemodialysis patients

End-stage renal disease (ESRD) causes growth retardation in children, and poor growth has been linked to worse outcomes. Recombinant human growth hormone (rhGH) can increase growth velocity and final adult height in pediatric ESRD patients. We aimed to identify clinical predictors of short stature (height standard deviation score (Ht SDS) <-1.88) and rhGH use in short stature pediatric hemodialysis patients. In 2002, the Centers for Medicare & Medicaid Services (CMS) Clinical Performances Measures (CPM) ESRD Project collected demographic, clinical and laboratory data as well as rhGH use on all in-center hemodialysis patients in the US aged <18 years. The odds ratios (OR) of short stature and rhGH use for individual predictors were determined by multivariate logistic regression modeling. Six-hundred and fifty-one (92%) of 710 eligible patients were included for analysis. Of these, 266 (41%) had Ht SDS <-1.88. After adjustment, short stature was predicted by congenital/urologic causes of ESRD ((OR 5.4; 95% confidence interval [CI], 2.1-13.8; p <0.001) in patients aged 10-14 years; (OR 2.8; 95% CI, 1.5-5.4; p <0.01) in patients aged 15-18 years) and increasing years on dialysis ((OR 1.2; 95% CI, 1.1-1.4; p <0.01) in patients aged 10-14 years; (OR 1.2; 95% CI, 1.1-1.4; p <0.001) in patients aged 15-18 years). Of 266 short stature patients, 214 (80.5%) had data on rhGH use. Of these, 80 (37%) had been prescribed rhGH. After adjustment, use of rhGH in short-stature patients was predicted by white race (OR 2.1; 95% CI, 1.1-4.0; p <0.05), increasing years on dialysis (OR 1.13; 95% CI, 1.05-1.22; p <0.01) and patients with BMI <16.6 kg/m(2) (OR 3.1; 95% CI, 1.2-8.4; p <0.05). Increasing age and level of intact parathyroid hormone were not associated with rhGH use among short stature patients. A significant proportion of pediatric hemodialysis patients have short stature. The majority of short-stature patients are not receiving rhGH. Patients with short stature who are white, have longer durations on dialysis and have lower BMI are more likely to receive rhGH.     

Skeletal status in children and adolescents with chronic renal failure before onset of dialysis or on dialysis

Bone status was assessed in 15 children and adolescents with predialysis chronic renal failure (CRF) and in 25 subjects with end-stage renal failure (ESRF). The mean age in the whole group was 14.6+/-3.2 years and CRF had been recognized 5.8+/-4.0 years earlier. The mean age, body size, duration of the disease and Tanner stages did not differ significantly between patients with predialysis CRF and ESRF. The control group consisted of 890 healthy subjects matched with patients for age. Bone mineral density (BMD) was measured by DPX-L (Lunar, Madison, WI) at the spine (s-BMD) and total body (TB-BMD); quantitative ultrasound (QUS) was performed by DBM 1200 (IGEA, Italy) at the hand phalanges (Ad-SoS). Laboratory investigations included the evaluation of intact parathyroid hormone (i-PTH), total and ionized serum calcium, and serum phosphate. In the whole group of patients the following mean values were obtained: Ad-SoS 1952+/-79 m/s (significantly lower than in controls, who had Ad-SoS 2022+/-85 m/s, p<0.05; the difference remained significant after adjusting for body mass index), s-BMD 0.87+/-0.22 g/cm2 ( Z-score -1.6), TB-BMD 0.92+/-0.12 g/cm2 ( Z-score -1.44), i-PTH 276+/-300 pg/ml, total calcium 2.46+/-0.19 mmol/l, ionized calcium 1.14+/-0.08 mmol/l, phosphate 1.68+/-0.61 mmol/l. Skeletal measurements correlated significantly with age, body size and Tanner stages (also after adjusting for age), while significant correlations of these parameters with the duration of CRF and laboratory investigations (except of correlations of i-PTH with Ad-SoS and with TB-BMD in predialysis patients) were not observed. None of the studied variables differed significantly between predialysis and dialysis patients. In conclusion, both predialysis and dialysis children and adolescents showed a decrease in BMD and quantitative ultrasound measurements. The severity of skeletal alterations was similar in the early phase (predialysis patients) and end stage (dialysis patients) of the disease and did not show a tendency to progress with CRF duration.     

Growth hormone therapy in chronic renal failure induces catch-up of head circumference

Growth of head circumference was studied along with height, weight, and body mass index (BMI) in 21 prepubertal patients with chronic renal failure (CRF) before and during recombinant human growth hormone (rhGH) treatment. CRF was present from birth in 15 patients, in the 6 others it was acquired and existing for at least 1 year. Five patients were on chronic dialysis, and 16 children were on conservative treatment with a median glomerular filtration rate of 17 ml/min per 1.73 m² at the start of rhGH therapy. rhGH was administered for 12 months in all patients, for 18 months in 19, and for 24 months in 12 patients. Mean height standard deviation score (SDS) increased significantly from –2.29 to –1.31 after 1 year and to –1.07 after 2 years. Mean BMI SDS was within the normal range throughout. Mean head circumference SDS improved significantly from –2.04 to –1.45 after 1 year and remained stable thereafter. Changes in head circumference differed between patients under 5 years and those over 5 years. In the former, the increase in head circumference SDS was already significant after 6 months of therapy, in the latter, significance was reached only after 1 year. It can be concluded that rhGH in CRF patients significantly improves head circumference SDS, albeit not to the same extent as height SDS. Received: 21 August 2000 / Revised: 21 February 2001 / Accepted: 26 February 2001     

Growth hormone treatment started in the first year of life in infants with chronic renal failure

Infants with chronic renal failure (CRF) are at high risk of experiencing severe growth retardation. We report a study of 12 infants with CRF who have been treated with recombinant human growth hormone (rhGH) since the age of 0.5 ± 0.3 years. A control group comprised 15 infants with less severe CRF who were being treated during the same period, but who did not receive rhGH. Despite the infants in the rhGH group had more severe renal failure, they grew at least as well as those in the control group and experienced catch-up growth that started earlier and was more sustained; they also gained more weight. Between the age of 0.5 and 2.5 years, the height standard deviation score (HtSDS) improved from −2.0 ± 1.2 to −0.9 ± 0.9 in the rhGH group (p < 0.005) and from −1.6 ± 1.6 to −1.0 ± 1.9 in the control group (p=non significant, n.s.). The average gain in HtSDS was +1.1 ± 0.8 in the treated group and +0.6 ± 1.4 in the control group (p = n.s.). During the same period, the weight SDS improved from −2.2 ± 0.9 to −0.6 ± 1.2 (p < 0.005) and from −1.9 ± 1.2 to −1.3 ± 1.2 (p=n.s.) in the treatment and control groups, respectively. Nutritional intake was similar in both groups, while parathyroid hormone levels tended to increase, although not significantly, after rhGH treatment (p=n.s.). The results of this pilot study suggest that very early treatment with rhGH in patients with early-onset CRF may improve growth.     

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.     

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.     

Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology

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. Members of the French Society of Pediatric Nephrology: J.L. André, A. Bensman, E. Bérard, J.P. Bertheleme, F. Bouissou, B. Boudailliez, F. Brou, M. Broyer, A. Burguet, G. Champion, P. Cochat, M. Dehennault, G. Deschênes, P. Desprez, R. Dumas, M. Fischbach, M. Foulard, M.T. Freycon, M.F. Gagnadoux, S. Gié, G. Guest, C. Guyot, G. Landthaler, M.P. Lavocat, C. Loirat, M.A. Macher, D. Morin, C. Mousson, P. Niaudet, H. Nivet, J.B. Palcoux, G. Picon, B. Roussel, M. Tsimaratos     

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.