[Radiologic differentiation of rhabdoid tumor from Wilms' tumor and mesoblastic nephroma]. / Bildgebende Differenzierung des Rhabdoidtumors vom Nephroblastom und mesoblastischen Nephrom.

Differentiation between rhabdoid tumor (RT) and mesoblastic nephroma (MN) and Wilms' tumor (WT) by imaging studies in babies and young children before histological confirmation is useful to start optimal treatment early. Typical radiologic criteria (crescent-shaped subcapsular liquid areas, tumor lobules, blurred tumor borders, metastasis in the lung, and regional lymph nodes) are described. The results of 26 MRI, 30 CT, and 22 ultrasound examinations of 49 patients (22 RT, 19 WT, and 8 MN, age 2-57 months) were analyzed. The above-mentioned radiologic criteria were classified with score values. The score value distribution was analyzed between the tumor entities and by two investigators.RT had significantly higher score values than the MN and WT. The difference between the two investigators was not significant. As a group RT differentiates from the group of WT and MN, but this is not possible in single cases with the radiologic criteria employed. Only if more signs are observed together in one case can a RT be presumed, which may indicate an early biopsy before chemotherapy.

Predictors of growth response to rhGH in short children before and after renal transplantation. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Many children with chronic renal failure (CRF) present with a reduced height and a reduced height velocity resulting in diminished final height irrespective of renal replacement therapy. Recombinant human growth hormone (rhGH) has become a new treatment modality for short renal patients, and the response to rhGH varies widely. In order to identify possible predictors of response to rhGH, the influence of sex, chronological age, bone age, pubertal status, height and height velocity at basal, target height, treatment modality for CRF, residual glomerular filtration rate (GFR), and steroid treatment was analyzed by single and multiple regression analysis in 49 children prior to and after renal transplantation. During the first treatment year with 28 to 30 IU rhGH/m2/week given by daily s.c. injections, height velocity was highest in patients on conservative treatment and lowest in patients on dialysis. Height velocity expressed in cm/year was inversely correlated with age (r = -0.63; P < 0.0001) and positively correlated with pretreatment height velocity (r = 0.65; P < 0.0001). The increment in height velocity SDS (chronological age) was significantly negatively correlated with the pretreatment height velocity SDS (chronological age) (r = -0.58, P < 0.001), indicating that at any given age the slowest growing children tended to respond best to rhGH treatment. It is concluded that the response to rhGH is significantly influenced by age, pretreatment height velocity, and treatment modality for CRF, whereas the influence of other variables is less important.

Long-term experience with growth hormone treatment in children with chronic renal failure.

After a decade of experience with recombinant human growth hormone (rhGH) in children with chronic renal failure (CRF), the long-term efficacy and safety of the drug is now established. In prepubertal children, partial catch-up growth is achieved during the first three treatment years, followed by sustained percentile-parallel growth. Discontinuation of rhGH treatment results in catch-down growth in 75% of patients. Treatment efficacy is inversely correlated with age and baseline height velocity, and positively influenced by genetic target height and residual renal function. Skeletal maturation is not accelerated, suggesting a true increase in final height potential. Side effects are limited to a stimulation of insulin secretion, which is not associated with changes in glucose tolerance, and occasional cases of benign intracranial hypertension. In summary, the advent of rhGH has opened a new era in the management of growth failure in CRF. Available evidence suggests that treatment should start in early childhood and early in the course of renal failure, and should be continued at least until renal transplantation. It remains to be seen whether the beneficial effect of rhGH on height observed during the prepubertal period will result in an eventual increase in adult height.

Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Fourteen patients on hemodialysis (HD) and 17 patients on continuous peritoneal dialysis (CPD) were treated with 28-30 IU/m2/week of recombinant human growth hormone (rhGH) for at least 12 months. The HD and CPD patient groups were comparable with regard to age, bone age, height standard deviation scores (SDS), and height velocity at start of treatment. During the first year of rhGH treatment, height velocity increased from 2.9 +/- 1.9 to 5.5 +/- 1.7 cm/year in the HD group and from 3.0 +/- 2.2 to 7.2 +/- 3.2 cm/year in the CPD group. The increase in growth rate was significant in both groups (p < 0.001), and tended to be significantly greater in the CPD than in the HD group (p = 0.09). The marked acceleration of growth under rhGH treatment resulted in an increase in relative height by 0.37 +/- 0.38 SDS in the HD group and by 0.47 +/- 0.69 SDS in the CPD group during the first treatment year. Seven HD and 7 CPD patients completed a second year of rhGH treatment. In these patients, height velocity dropped to 3.6 +/- 2.7 cm/year (HD) and 3.6 +/- 2.3 cm/year (CPD), respectively during the second treatment year. We conclude that rhGH treatment accelerates growth in children both on HD and CPD. The treatment response tends to be greater in CPD compared to HD patients. The efficacy of treatment decreases considerably during the second treatment year.

[Management of high blood pressure in children and adolescents: Recommendations of the European Society of hypertension]. / Manejo de la hipertensión arterial en niños y adolescentes: recomendaciones de la Sociedad Europea de Hipertensión.

Hypertension in children and adolescents has been gaining ground in cardiovascular medicine, mainly due to the advances made in several areas of pathophysiological and clinical research. These guidelines arose from the consensus reached by specialists in the detection and control of hypertension in children and adolescents. Furthermore, these guidelines are a compendium of scientific data and the extensive clinical experience it contains represents the most complete information that doctors, nurses and families should take into account when making decisions. These guidelines, which stress the importance of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, should act as a stimulus for governments to develop a global effort for the early detection and suitable treatment of high pressure in children and adolescents. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Growth hormone treatment in short children with chronic kidney disease.

UNLABELLED: Growth hormone (GH) has been used for treatment of impaired growth in children with chronic kidney disease (CKD) for nearly 17 years. Controlled and open-label studies have shown that GH is highly effective in improving growth velocity and adult height. The growth response is negatively correlated with age and height at start and time spent on dialysis treatment; it is positively correlated with dose and duration of treatment and the primary renal disease (renal hypodysplasia). In children with renal transplants, corticosteroid treatment is an additional factor negatively influencing spontaneous growth rates. However, GH treatment is able to compensate corticosteroid-induced growth failure. GH treatment improved final height by 0.5-1.7 standard deviation score (SDS) in various studies, whereas the control group lost about 0.5 SDS in comparable time intervals. These variable results are explained in part by the factors mentioned above. The adverse events are comparable to those in non-CKD children treated with GH. CONCLUSION: GH treatment is safe and highly effective in improving growth and final height of short children with all stages of CKD. The highest treatment success is obtained if treatment is started at an early age and with relatively well-preserved residual renal function and continued until final height.

Puberty in chronic renal failure.

Puberty is a period of transition characterized by a sequence of profound physical and psychological changes leading to full sexual maturity. This process is driven and orchestrated by the awakening of the gonadotropic hormone axis. Chronic renal failure and its treatment may interfere with the onset and progress of puberty by numerous mechanisms including endocrine, metabolic and neuropsychological abnormalities, and drug effects. On average, the onset of puberty is delayed by 2 years in children with chronic renal failure, even after successful transplantation. Moreover, pubertal height gain is only 50% of that observed in healthy children. In this report, we discuss the endocrine mechanisms underlying these alterations and highlight new therapeutical options for pubertal growth failure.

Body mass index and percentage fat mass in healthy German schoolchildren and adolescents.

OBJECTIVE: To provide reference data for obesity indices in Mid-European schoolchildren and adolescents, to evaluate the usefulness of body mass index (BMI) as an indicator of obesity in children, and to analyse the patterns of fat accumulation during childhood. DESIGN: Cross-sectional observational study in 2554 healthy schoolchildren and adolescents (age, 6-19 y) living in Heidelberg, Germany in 1989/1990. Centile charts for BMI and skinfold-derived percentage body fat mass (PFM) were constructed using Cole's LMS method for normalised growth standards. RESULTS: The BMI centile values of German children ranged higher than French, lower than North American and Italian, and similar to Swedish and British children. While BMI steadily increased with age, PFM was markedly lower in peripubertal than in pre- and postpubertal boys. BMI predicted PFM with reasonable precision in girls (r=0.84), and in obese boys (r=0.58), but not in the leaner two thirds of the male population (r=0.01, NS). The 75th BMI percentile was the most appropriate cutoff value to screen for the 15% most obese patients by PFM (sensitivity: 82%, specificity: 85%). The pattern of the trunk-to-extremity skinfold ratio across childhood suggested that the typical adult distribution of central and peripheral fat is achieved in mid puberty in girls, but not before the end of adolescence in boys. CONCLUSIONS: The major differences observed between BMI charts obtained in different countries underline the need for population-specific reference data. BMI is of limited usefulness in predicting relative fat mass in individual children. The developmental pattern of fat accumulation and distribution during adolescence is highly dynamic and gender-specific.

Disproportionate growth following long-term growth hormone treatment in short children with X-linked hypophosphataemia.

UNLABELLED: Three short prepubertal children with X-linked hypophosphataemia were treated with 1 IU recombinant human growth hormone (rhGH)/kg per week sc in addition to calcitriol and phosphate supplementation over a period of 3 years. Improvement of height standard deviation score (SDS) ranged from 1.0-1.7 SD based on an increase in sitting height of 1.5-2.9 SD, whereas subischial leg length improved only slightly by 0.3-0.9 SD. In all three patients, renal phosphate threshold concentration increased slightly and transient hyperparathyroidism was noted. CONCLUSION: Treatment of stunted children with X-linked hypophosphataemia is effective in improving growth velocity, but appears to aggravate the pre-existent disproportionate stature of such children.

Body growth in children with polycystic kidney disease. Arbeitsgemeinschaft für Pädiatrische Nephrologie.

We analysed the body growth of 121 prepubertal children with polycystic kidney disease participating in a longitudinal multicentre study. The patients were followed from an age of 1 to 9 years in girls and 1 to 10 years in boys over a mean period of 3.6 years. Children with end-stage renal disease were excluded. Fifty-four patients had the autosomal dominant form of the disease and 67 the autosomal recessive form. At last observation, 2% of patients with the dominant form and 28% of those with the recessive form had an estimated glomerular filtration rate of < 60 ml/(min 1.73 m2). At first observation, the mean height SD score (SDS) in patients with the dominant form was almost the same as in controls, whilst in those with the recessive form it was significantly decreased (girls -0.82 SDS, boys -0.68 SDS, p < 0.001). During the follow-up the height SDS decreased slightly in both groups (NS). In patients with autosomal recessive kidney disease the degree of growth retardation appeared to be related to renal function: at last observation the height of girls with an estimated glomerular filtration rate of < 60 ml/(min 1.73 m2) was more retarded than that of boys (mean -2.1 SDS versus -1.5 SDS, NS). The height SDS and renal function at last observation correlated in girls (r = 0.83, p < 0.001) but not in boys (r = 0.55) with the recessive form. No correlation was found between the height SDS and hypertension. The weight-for-height SDS at onset was significantly reduced in patients with the recessive form with decreased renal function. Our data suggest that the autosomal recessive, but not the dominant, form of polycystic kidney disease is associated with early growth retardation, which seems to be more severe in girls, probably due to the more rapid deterioration of renal function.

The use of recombinant human growth hormone in short children with chronic renal failure.

Regulation of the somatotropic axis is altered in chronic renal failure (CRF) resulting in a secondary syndrome of growth hormone (GH) insensitivity. Secretion of growth hormone estimated by deconvolution analysis is low normal in prepubertal patients and reduced in late pubertal children with CRF. Basal and integrated GH serum concentration measured by RIA is increased due to reduced renal metabolic clearance, whereas the fractional urinary excretion is increased due to damage of renal tubular cells. GH receptor mRNA is decreased (rat) and the serum concentration of GH binding protein (BP) activity is low (man). Insulin-like growth factor (IGF)-1 production rate is reduced, whereas serum concentrations of IGFBPs are increased secondary to reduced renal metabolic clearance. This results in a reduction of free, active IGF-1. Treatment with GH induces a rise in serum IGF-1 concentration and normalizes IGF bioactivity. Clinical studies in prepubertal children demonstrated a dramatic rise in height velocity during the first treatment year and to a lesser extent during the following years. In children on conservative treatment prior to dialysis, mean height SDS improved by 1.5 within two years and by 2.0 within four years. Patients with renal allografts responded in a similar way. Age and pretreatment height velocity SDS are confounding variables for the response to GH. Renal function seems not be altered by recombinant human (rh) GH in patients with CRF, and the number of renal allograft rejection crises seems not to be substantially increased under rhGH treatment in allograft recipients.

Assessment of total body water in paediatric patients on dialysis.

BACKGROUND: Various anthropometric techniques are used to assess total body water in children on dialysis; however, their predictive accuracy and precision has not been validated. METHODS: We compared total body water measurements obtained by deuterium oxide (D2O) dilution with predictions of total body water from (1) height and weight, (2) skinfold measurements, and (3) bioelectrical impedance analysis, using previously published formulae for healthy children. Measurements were performed in 14 patients on peritoneal and in nine patients on haemodialysis, aged 4-22 years. RESULTS: In the total population of dialysed patients, weight was the strongest single predictor of total body water (R2 = 0.93), followed by the resistance index (RI = height2/impedance; R2 = 0.85) and height (R2 = 0.93). A prediction formula based on height and weight predicted total body water with a residual mean square error (RMSE) of 1.97 1 (coefficient of variation (CV) = 10.0%) and with a systematic overestimation of true total body water by 0.4%. A prediction equation based on skinfold measurements yielded a total body water estimate with an RMSE of 2.15 1 (CV = 10.5%) and overpredicted true total body water by an average of 2.2%. Using three published prediction equations incorporating RI, RMSEs of 2.78 1 (CV = 14.1%) with a mean under- or overestimation of true total body water by 6.9, 7.1, and 0.8% respectively, were achieved. The prediction of total body water was optimized by linear combinations of RI or the log-transformed sum of four skinfolds (logsum) with weight by the following equations: total body water (1) = 9.97 - 3.13 x logsum (1) +0.59 x weight (kg) (R2 = 0.951; RMSE = 1.67 1; CV = 8.17%). total body water (1) = 1.99 + 0.144 x RI (Ohm/cm2) (2) + 0.40 x weight (kg) (R2 = 0.949; RMSE = 1.67 1; CV = 8.53%). The fit of these prediction formulae, which were derived from the total population, did not differ significantly between haemo- and peritoneal dialysis patients or between boys and girls. CONCLUSIONS: Both skinfold measurements and bioelectrical impedance analysis can be used to improve the height- and weight-based prediction of total body water in children on dialysis.

Growth hormone as a new treatment modality for short children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Recombinant human growth hormone (rhGH) has become a new treatment modality for short children with chronic renal failure (CRF) and after renal transplantation. The rationale for high-dose rhGH treatment is the insensitivity of the uremic organism to GH. As the insensitivity to GH is expressed more in end-stage renal failure than in earlier stages of CRF, patients on dialysis respond less to rhGH. In transplanted children, rhGH can counterbalance the growth-depressing effects of corticosteroids. In prepubertal children, rhGH improves the height standard deviation score by a mean of +2 within 5 years. The effect of rhGH treatment on final height remains to be studied.

Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

BACKGROUND: Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. METHODS: We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. RESULTS: The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. CONCLUSIONS: Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

Long-term treatment with growth hormone in short children with nephropathic cystinosis.

OBJECTIVE: The objective was to assess the efficacy and safety of growth hormone (GH) treatment in severely growth retarded children with nephropathic cystinosis during conservative treatment and during renal replacement therapy. STUDY DESIGN: The design was an open-labeled prospective trial with a run-in period of 1 year. RESULTS: A total of 74 children with cystinosis (age 3.0 to 18 years) were treated with GH over a mean period of 3.1 years (range 1 to 10 years); 52 patients were receiving conservative treatment (mean age 7.1 years), 7 were receiving dialysis (12.5 years), and 15 had received a renal transplant (14.8 years). The mean standardized height (SD score) was -4.0 in the conservative treatment group, -4.4 in the dialysis group, and -4.9 in the renal transplant group. During the first treatment year, height velocity doubled in the conservative treatment group, increased by 80% in the dialysis group, and increased by 45% in renal transplant group. Within 3 years the height SD score increased by +1.6 (P <.001) in prepubertal patients receiving conservative treatment, and percentile parallel growth was maintained thereafter. These effects of GH were less expressed in peripubertal patients receiving renal replacement therapy. No major side effects were observed. CONCLUSION: Long-term GH treatment is safe and effective in young children with nephropathic cystinosis. GH treatment should be started early in the course of the disease if adequate nutrition and cysteamine treatment do not prevent growth retardation.

Impact of ACE I/D gene polymorphism on congenital renal malformations.

To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n = 59), other congenital or hereditary diseases (n = 23), or acquired glomerular disorders (n = 13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal 'survival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m2 as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n = 163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P < 0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P < 0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P < 0.001) and gross proteinuria (RR 4.7, P < 0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria.

Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

To evaluate the metabolic effects of long-term treatment with recombinant human (rh) GH in short children with chronic renal failure (CRF), annual oral glucose tolerance tests (oGTT) during rhGH therapy for up to 5 y in 53 prepubertal children with CRF on conservative treatment, dialysis, and after renal transplantation were compared with that of 12 age-matched children treated with rhGH for idiopathic short stature. At the start of rhGH treatment, fasting values of glucose, insulin, glycosylated Hb A (HbA1C), triglycerides, cholesterol, glucose, and insulin responses during oGTT were significantly elevated in all patient groups compared with control subjects (p < 0.001). In the total population, fasting and 2-h postprandial glucose concentrations were inversely correlated with GFR and positively with age and methylprednisolone dosage in transplanted patients. Fasting insulin levels were positively correlated with body mass index and inversely with GFR. RhGH treatment was not associated with a change in fasting or stimulated glucose concentrations in any treatment group throughout the observation period. In contrast, serum insulin levels increased during the first treatment year in all groups, resulting in a more marked elevation of integrated insulin levels in transplant (1402 +/- 179 pM) and dialysis (1025 +/- 114 pM) patients compared with conservatively treated patients (829 +/- 94 pM), and control subjects (719 +/- 89 pM) (p < 0.01). Hyperinsulinemia persisted in all treatment groups for up to 5 y of follow-up. In conclusion, age, renal function, and obesity are the major independent predictors of glucose tolerance in children with CRF. Long-term rhGH treatment does not affect glucose tolerance, but aggravates the preexisting hyperinsulinemia in children with end-stage renal disease. In concert with the dyslipidemia of uremia, the rhGH-promoted hyperinsulinemia may contribute to the long-term risk for premature atherosclerosis in patients with childhood onset CRF.

Pharmacokinetics of a new microemulsion formulation of cyclosporin A (Neoral) in young patients after renal transplantation.

Pharmacokinetics of the new galenic formulation of cyclosporin A, Neoral, (Sandoz) was examined in 12 stable young patients after renal transplantation. Six of these patients were tested before and 4 weeks after switching from the standard formulation Sandimmun to Neoral. No significant changes were observed in trough levels, Lmax, Cmax, and AUC0-12 h, but the absorption rate constant (Ka) increased (P = 0.03). Glomerular filtration rate, as assessed by inulin clearance, increased by more than 10% in three patients and decreased in two, and was usually associated with a respective drop and rise in Cmax and AUC0-12 h of cyclosporin A. The large interindividual variability in the response to the conversion to the new formulation points to a need for close monitoring of cyclosporin A trough levels and renal function after switching from Sandimmun to Neoral in this age group in order to avoid nephrotoxicity.

Bilateral renal venous thrombosis in a neonate associated with resistance to activated protein C.

Renal venous thrombosis (RVT) is a serious complication of neonates. In most cases the underlying cause of RVT remains unclear. Here we report a neonate with bilateral RVT and adrenal haemorrhage associated with a heterozygous mutation of the gene encoding for clotting factor V, resulting in resistance to activated protein C. Vigorous thrombolytic therapy with urokinase followed by recombinant tissue plasminogen activator dissolved the thrombus in the inferior vena cava and restored perfusion of both kidneys. However, a haemorrhagic rupture of the right kidney occurred, requiring emergency nephrectomy. Despite reperfusion of the left kidney and resumption of urine output, the patient remained dialysis dependent. Due to persistent adrenal insufficiency, long-term substitution of hydrocortisone was necessary. The patient was prophylactically treated with coumarin during the first 6 months of life and is now waiting for renal transplant at the age of 1 year.