Growth failure in children with renal disease : incidence, pathophysiology, new perspectives with growth hormone therapy

Stunted growth is a serious problem for children with chronic renal insufficiency (CRI). Advances in the treatment of renal insufficiency, including dialysis and renal transplantation, have greatly improved the survival rate for these patients. Consequently the failure to grow has become a major issue. Unfortunately. despite intensive medical care, optimized nutrition. vitamin D and mineral supplements, and dialysis, it has proved impossible to improve height velocity.' Growth retardation tends to occur when the glomerular filtration rate drops below 20-30 ml/min/L73m'. Infants with CRI secondary to congenital renal abnonnalities are particularly prone to growth failure during the first years of life. When CRI is first diagnosed in a child, the child's height will often lie below the third height percentile for age. It has been reported that nearly 40% of children that enter dialysis have a height below the third height percentile

Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency

To assess the effects of long-term continuous GH treatment on body composition, blood pressure (BP), and lipid metabolism in children with short stature born small for gestational age (SGA), body mass index (BMI), skinfold thickness measurements, systemic BP measurements, and levels of blood lipids were evaluated in 79 children with a baseline age of 3-11 yr with short stature (height SD-score, < -1.88) born SGA (birth length SD-score, < -1.88). Twenty-two of the 79 children were GH deficient (GHD). All children participated in a randomized, double-blind, dose-response multicenter GH trial. Four- and 6-yr data were compared between two GH dosage groups (3 vs. 6 IU/m2 body surface/day). Untreated children with short stature born SGA are lean (mean BMI SD-score, -1.3; mean SD-score skinfolds, -0.8), have a higher systolic BP (SD-score, 0.7) but normal diastolic BP (SD-score, -0.1), and normal lipids (total cholesterol, 4.7 mmol/L; low-density lipoprotein, 2.9 mmol/L; high-density lipoprotein, 1.3 mmol/L) compared with healthy peers. During long-term continuous GH treatment, the BMI normalized without overall changes in sc fat compared with age-matched references, whereas the BP SD-score and the atherogenic index decreased significantly. Although the mean 6-yr increase in height SD-score was significantly higher in the children receiving GH treatment with 6 IU/m2 x day (2.7) than in those receiving treatment with 3 IU/m2 day (2.2), no differences in the changes in BMI, skinfold measurements, BP, and lipids were found between the GH dosage groups. The pretreatment SD-scores for BMI, skinfold, and BP, as well as the lipid levels, were not significantly different between GHD and non-GHD children, but after 6 yr of GH treatment the skinfold SD-score and BP SD-score had decreased significantly more in the GHD than in the non-GHD children. Our data indicate that GH treatment has at least up to 6 yr positive instead of negative effects on body composition, BP, and lipid metabolism. In view of the reported higher risk of cardiovascular diseases in later life in children born SGA, further research into adulthood remains warranted

Fatness and muscularity as risk indicators of child mortality in rural Congo

OBJECTIVES: To examine the relationship of anthropometrical indicators of fatness and muscularity with mortality in children in a rural African community. BACKGROUND: A prospective cohort study was carried out in the rural health zone of Bwamanda, Northern Congo using a random cluster sample of 5167 children, aged 0-5 years. MAIN OUTCOME MEASURES: Short- and long-term mortality rates, being deaths within 3 months and deaths in 3-month periods observed 3-30 months after enrolment. Rates of all cause mortality and of mortality from kwashiorkor or marasmus, by level of baseline fatness and muscularity. Indicators of fatness and muscularity were obtained by correcting anthropometric arm fat and arm muscle areas for age, sex, weight and height. RESULTS: The relationship of both the fatness and muscularity scores with short-term mortality was marked by a clear threshold (-0.5 SDS) below which there was a significant rise in mortality from all causes as well as from kwashiorkor and marasmus. These excess mortalities were also found in normal weight children. Fatness and muscularity scores remained significant determining factors of short-term mortality in a multiple logistic regression analysis with sex, age, season and weight-for-age. A ROC curve analysis showed that fat and muscularity scores had better predictive abilities than weight-for-age. Low fat status had a bad prognosis on the long-term in underweight children. CONCLUSIONS: Measures of current nutritional status should not be based on weight indices alone. Objective and/or clinical evaluation of fat and muscle status (also in normal weight children) should be added in order to detect a higher proportion of malnourished children and to more accurately evaluate mortality risk

Validation and calibration of the Kabi Pharmacia International Growth Study prediction model for children with idiopathic growth hormone deficiency

In 1999 a model was published for prediction of growth in children with idiopathic GH deficiency (IGHD) during GH therapy, derived using data from the Kabi Pharmacia International Growth Study (KIGS) database (Pharmacia \\|[amp ]\\| Upjohn, Inc., International Growth Database). We validated and calibrated this KIGS model for growth in the first year of GH therapy using data from 136 Dutch children with IGHD. Observed vs. predicted outcomes were plotted, and the fitted regression line was significantly different from the line of identity (P = 0.03). It appeared that the predictions were too extreme: relatively low predictions were too low, relatively high predictions were too high. This is a well known phenomenon in the context of prediction models, called overoptimism. For valid application to other data the KIGS predictions should be calibrated. Calibrated predictions are obtained using Y(cal) = Y(orig) + (2.153 - 0.192 x Y(orig)), where Y(cal) is the calibrated prediction, and Y(orig) is the KIGS prediction. The calibrated prediction will be higher than the original KIGS prediction when the original prediction is less than 11.2 cm/yr and will be lower otherwise. The variability of the prediction errors of the calibrated predictions was positively related to the value of the prediction (P < 0.001), described by the equation SD(pred err) = -1.017 + 0.286 x Y(cal). Our calibrated model will give better predictions for children with IGHD fulfilling the same criteria

Patient Acceptance, Ease of Use, and Preference for Norditropin NordiFlex with NordiFlex PenMate: Results from an Open-Label, User Survey of Everyday Use

In this 12-week open-label, uncontrolled study, patients (n = 85; mean [SD] age 11.2 [3.95] years) were trained to use an injection device with an automatic needle insertion accessory (NordiFlex/NordiFlex PenMate: Novo Nordisk A/S, Bagsvaerd, Denmark) for growth hormone (GH) injection. The opinions of patients and the physicians/nurses who trained patients on device were recorded by questionnaire. Most (88.4%) patients reported that the device was “very easy/easy" to use. The majority (82.4%) of patients were “very satisfied/satisfied" with the device and 64% wished to continue its use. Device training instructions were reported as “very easy/easy" by 96.1% of physicians/nurses, and 65.8% of participants could use the device after ≤10-minute training. In this study, NordiFlex PenMate was well accepted by patients and medical staff. Patients had a high opinion of the device and over half wished to continue its use. High patient acceptance may facilitate treatment adherence optimizing treatment outcomes

Puberty in growth hormone-treated children born small for gestational age (SGA)

Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups