University Cl~ildret~'~ Ilospital. Ilci(lc~lhc~r,y, Gcrrtlro~y /F.S., ;\I.G., K.S../ ut~d hr~rcI.ar Rcscw-ch Coltrc~.Kurl.tr~rlrc, Gcrr)lunjv [..I .%.I ABSTRACT. Despite the increasing use of tetrapolar TBK, total body potassium whole-body bioelectric impedance (BI) analysis in the as-CV, coefficient of variation sessment of body composition, its usefulness in estimating RhISE, root mean square error fat-free mass (FFR.1) has not been evaluated in comparison with conventional skinfold anthropometry in children. We therefore compared I) the intraobserver and interobserver reproducibility of BI and skinfold measurements and the Within the past few years, BI analysis has gained wide use in derived FFhl estimates, and 2) the predictability of FFhI the assessment of body composition. The method appears para s calculated from measurements of total body potassium ticularly suitable for use in children, because the measurements (TBK) using ' "K spectrometry by equations based on either are fast, noninvasive, painless, and require little subject cooper-BI or skinfold measurements in 112 healthy children, ation. The BI technique is based on the difference in specific adolescents, and young adults aged 3.9 to 19.3 y. best-resistance to an electrical current between aqueous and nonfitting equation to predict TBK-derived FFhl from BI and aqueous compartments within the body. Validation studies have other potential independent predictors was developed and shown the accuracy and precision of the technique to be at least cross validated in two randomly selected subgroups of the comparable with conventional anthropometric methods such as study population by stepwise multiple regression analysis. skinfold thickness measurements in both adults and children Although the technical error associated with BI measure-(1-4). ments was much smaller than that of skinfold measure-The few studies performed so far in children suggest that the mcnts, the reproducibility of BI-derived FFhl estimates changing proportions of body fluid compartments during child-(intraobserver coefficient of variation [CV], 0.39%; inter-hood may require the use of specific pediatric prediction equaobserver CV, 1.2370) was only slightly better than that of tions (4-7). However, the validation methods used so far are FFhI estimates obtained by use of weight and two skinfold difficult to apply in smaller children or rely on a number of measurements (0.62% and 1.39%, respectively). 'l'he cross unverifiable assumptions. Densitometric underwater weighing validation procedure yielded the following best-fitting pre-and respirometric assessment of residual lung volume require diction equation: FFhI = 0.65. (height2/impedance) + full subject cooperation. In addition, the specific density of the 0.68.age + 0.15 (Rz = 0.975, root mean square error = FFM seems to change during childhood; variable-density FFM 1.98 kg, CV = 5.8%, 95% limits of agreement = -1 1.1% models have been applied but are hypothetical (4, 8). Isotope to +12.470). Conventional anthropometry, using publi...

The clinical course of 66 boys and 49 girls with autosomal recessive polycystic kidney disease recruited from departments of paediatric nephrology was investigated over a mean observation period of 4.92 years. This is a selected study group of children from departments of paediatric nephrology who in most cases survived the neonatal period, since birth clinics did not participate. The median age at diagnosis was 29 days (prenatal to 14.5 years). We observed decreased glomerular filtration rates (GFRs) in 72% (median age at onset of decrease of GFR < 2 SD, 0.6 years; range, 0-18.7 years), and 11 patients developed end-stage renal disease. Hypertension requiring drug treatment was found in 70% (median age at start of medication, 0.5 years; range, 0-16.7 years). Kidney length was above the 97th centile in 68% of patients, and kidney length did not increase with age or deterioration of renal function. Urinary tract infections occurred in 30%, growth retardation in 25%, and clinical signs of hepatic fibrosis were detected in 46%. Thirteen patients (11%) died during the observation period, 10 of them in the first year of life. There was a statistically significant sex difference in terms of a more pronounced progression in girls. The survival probability at 1 year was 94% for male patients and 82% for female patients (p < 0.05) in this study. Urinary tract infections occurred more frequently in girls (p < 0.025) and were observed earlier. In addition, more girls had impaired renal function, developed end-stage renal disease and showed growth retardation; these differences, however, were not significant. For the children in this study, however, our results indicate that the long-term prognosis in the majority of cases is better throughout childhood and youth than often stated.

We studied the long-term outcome of 64 children with biopsy-proven Schönlein-Henoch purpura (SHP) nephritis over 1-23 years of follow-up. Overall renal survival 10 years after onset was 73%. Multivariate logistic regression analysis identified initial renal insufficiency (P=0.004), nephrotic syndrome (P=0.037), and the severity of histological alterations, as defined by the proportion of glomerular crescents (P=0.051), as significant independent predictors of progressive renal failure. Four patients followed for more than 19 years showed glomerular damage after transient recovery. Eight children with crescentic nephritis associated with a rapidly progressive course and/or persistent nephrotic syndrome were treated by at least seven sessions of plasma exchange (PE) within 16 weeks of onset of purpura. During treatment serum creatinine levels dropped in each patient from a mean of 2.3 to 1.1 mg/dl, followed by a rebound increase. Repeated courses of PE in 5 patients produced comparable responses. Four patients undergoing PE reached end-stage renal disease at 1.2.-3.7 years after onset, whilst 3 finally were in preterminal renal failure (creatinine 3.2-6.1 mg/dl after 7-13.5 years), and 1 patient reached a normal glomerular filtration rate. Our experience suggests that initial renal insufficiency is the best single predictor of the further clinical course in children with SHP nephritis. Early PE appears to delay the progression in some patients with severe, rapidly progressive forms of the disease.

We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.

No abstract

Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS.

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 1989a1990. 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%, speci®city: 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-speci®c 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-speci®c.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the major hereditary nephropathies in children predominantly presenting in early childhood. The clinical picture is variable but there is a fatal outcome in many cases. We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21-cen with no evidence for genetic heterogeneity among different clinical phenotypes. Linkage was confirmed using six adjacent microsatellite markers and the highest lod score of 7.42 was obtained with D6S272 at theta = 0.00. Our findings should lead to more accurate forms of prenatal diagnosis than those currently available using ultrasound.