Rosario Di Toro

HIGH INCIDENCE OF A GENERALLY SMALL KIDNEY AND PRIMARY VESICOURETERAL REFLUX

PURPOSE We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux. MATERIALS AND METHODS We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively. RESULTS We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively). CONCLUSIONS When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

Interaction of Trace Elements in a Longitudinal Study of Human Milk from Full-Term and Preterm Mothers

Concentrations of 8 trace elements (Fe, Cu, Zn, Se, Br, Pb, Rb, and Sr) at different lactation time were measured by the PIXE multi-elemental technique. Time dependence and interelement correlations were studied. A total of 200 milk samples from 32 lactating mothers were supplied from 2 to 120 d after delivery of 26 full-term and 6 preterm infants. All elements showed a lognormal frequency-distribution. The Fe, Cu, Zn, and Se contents in preterm milk were found to be somewhat different with respect to full-term milk. Cu, Zn, Se, Br, Pb, and Rb concentrations declined with lactation time, both in pre- and full-term samples. Sr and Fe contents did not show any change with time. Detailed analysis of data by partial correlation and multiple regression methods was performed. No substantial differences between preterm and full-term samples were found in the results of partial correlation analysis. Cu and Zn were found to be correlated with lactation time, whereas the measured time dependence for the other elements has to be attributed to the effect of the existing interelement correlation. All the measured elements appeared to be correlated with at least one other element. In particular, Se was inversely correlated with Zn and directly with Cu. The zinc and copper contents in milk can therefore depend on the variation in the mother selenium intake.

Enhanced detection of vesicoureteric reflux with isotopic cystography

Abstract We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

Trace elements in hair of healthy children sampled by age and sex

Hair trace element (TE) (Cr, Mn, Fe, Zn, Cu, Br, Rb, Sr, Pb) levels from 336 healthy subjects were measured by the Proton-Induced X-ray Emission (PIXE) method. The subjects were divided in three groups: 157 full-term neonates (75 male and 82 female), 86 children (41 male and 45 female) ages 6 to 11 yr, and 93 adolescents (51 male and 42 female) 11 to 16 yr old. Cu, Zn, Cr, and Br show an increase from birth to 8 yr and then decrease. Fe, Mn, and Sr strongly decrease up to 8 yr and then remain almost stable. Sex differences are present in Fe, Zn, and Br of children and in Cu, Cr, and Br of adolescents.

Zinc, copper, and iron in obese children and adolescents

Abstract Zinc, copper and iron content in different cells and fluids of 143 obese children and adolescents were compared with the content in the same matrices of 164 healthy controls matched for age, sex, ethnic origin, nutritional habit and income level. The measures obtained were correlated with some anthropometric and biological parameters currently considered as cardiovascular risk factors. Serum zinc level was found to be lower in obese than in normal subjects and inversely correlated with skinfold thickness. The serum copper concentration was inversely related to the age, triglycerides serum level and directly with skinfold thickness. Serum triglyceride concentration was higher in obese than in age-matched controls and positively correlated to total cholesterol. There was also a direct correlation between serum zinc and copper concentration, between serum iron and triglycerides. BMI correlated directly with skinfold thickness. No significant correlation was obtained between trace elements content in the studied matrices and total cholesterol or its fractions.

Renal Calyceal Microlithiasis: Clinical Presentation May Precede Sonographic Evidence

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occuring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria. Clin Pediatr. 1999;38:521-524

Urinary sodium and potassium excretion in idiopathic hypercalciuria of children.

Background: An increased spot urine Na/K ratio (UNa/K) has been found to be related to urinary stone disease in adults with a history of nephrolithiasis and in children with idiopathic hypercalciuria (HC). However, the respective role played by Na and K excretion in the rise of the UNa/K in growing individuals is not well clarified. Methods: The urinary excretion of Na and K was evaluated in fasting morning and 24-hour urine samples of 37 consecutive children with HC and of 21 previously HC children who were normocalciuric at the time of the study (ExHC). None of them had received any dietary or specific drug prescription. Results: In the HC and in the ExHC group, respectively, the Na excretion was 4 ± (SD) 2.4 and 2.9 ± 1.3 mmol/kg/day (p = 0.009); the K excretion was 1.1 ± 0.4 and 1.2 ± 0.7 mmol/kg/day (p = 0.86); the fasting UNa/K was 3 ± 1.6 and 2.1 ± 1 mmol/mmol (p = 0.044), and the 24-hour UNa/K was 4.2 ± 3.9 and 2.8 ± 1.5 mmol/ mmol (p = 0.045). The 24-hour UNa/K was significantly higher than the fasting UNa/K in both HC (p = 0.002) and ExHC (p = 0.002) subjects. The 24-hour UNa/K significantly increased with age in both HC (p = 0.02) and ExHC (p = 0.015) children. The K excretion significantly decreased with age in HC (p = 0.0001) and ExHC (p = 0.005) subjects, as well as with body weight gain in HC (p = 0.005) and ExHC (p = 0.0001) children and with increasing body height in HC (p = 0.006) and ExHC (p = 0.001) subjects. In neither group was the K excretion significantly related to body mass index Z score nor to height Z score. No significant relation resulted between Na excretion and age, body weight and height, and body mass index Z score and height Z score. Conclusions: HC children have a higher Na excretion as well as a higher fasting and 24-hour UNa/K than ExHC children, but no different K excretion. Meals are accompanied by a significant rise in UNa/K. The rise in UNa/K with age is mostly due to a decrease in K excretion which possibly depends on childhood body growth.

Body growth in early diagnosed vesicoureteric reflux.

Abstract Body growth was studied in 32 subjects with vesicoureteric reflux (VUR), diagnosed following the prenatal finding of urinary tract dilatation, who had normal renal filtration function and who received antibacterial prophylaxis by the first few days of life. They were followed for 1–5 years (mean 2.3 years). Most had persistent VUR during the 1st year of life. Body growth performance was compared with that of 94 subjects with VUR diagnosed and treated by us after the neonatal period. During the follow-up period, none of the patients with prenatally detected VUR had a height Z score below –2, nor a weight-for-height index below 90%, and 1 had variations in height Z score ≥1. The difference in the percentage of patients with prenatally detected VUR (1/32) and those with VUR diagnosed and treated after the neonatal period (20/94) who had variations in height Z score ≥1 was significant (P=0.035). Patients with prenatally detected VUR and normal renal filtration function, given antibacterial prophylaxis by the first few days of life, have normal body growth, although VUR still persists.

Evaluation of leptin protein levels in patients with Cooley's anaemia

Endocrine disorders related to toxic effects of iron overload, such as short stature, delayed puberty and hypogonadism, represent major problems in both adolescent and adult thalassaemic patients. It has been suggested that gonadal dysfunction in these patients might be characterized mainly by a neuroendocrine dysfunction resulting in impaired hypothalaemic releasing hormone production, which is inadequate for proper pituitary stimulation (Kattamis & Kattamis, 1995). Pulsatile gonadotrophin releasing hormone (GnRH) treatment seems to re-establish, at least partially, the correct pituitary–gonadal function. Leptin, a recently discovered adipocyte-derived hormone, acts primarily at the hypothalamus, where it has effects on appetite, energy expenditure and the neuroendocrine axes. Leptin-deficient mice exhibit a complex phenotype which includes hypogonadism, impaired sexual maturation and infertility due to hypothalamic–pituitary hormone failure (Flier & Maratos-Flier, 1998). Exogenous leptin allows the recovery of the reproductive function. Recently, a related man and woman with congenital leptin deficiency have been described. Both showed hypogonadism (i.e. small penis and testis, primary amenorrhoea, respectively) of hypothalamic origin, suggesting that leptin not only controls body mass but may also be necessary to initiate human puberty (Strobel et al, 1998). To evaluate leptin levels in thalassaemic patients, blood samples were collected after an overnight fast from 162 patients with Cooley’s anaemia, 78 males (age: mean 19 6 7 years, range 5–39) and 84 females (age: mean 20 6 12 years, range 6–41) and from 138 normal subjects, matched for gender, age and body mass index (BMI). Leptin was measured by a commercial radioimmunoassay (Linco Research Inc., St Louis, Mo.). BMI was calculated as weight (kg) divided by height (m) squared. Mean leptin concentration was 2·69 6 1·23 ng/ml in thalassaemic males; this value appeared to be significantly lower (P <0·0005) than in controls (6·86 6 2·71 ng/ml). Although thalassaemic females also had lower leptin levels (6·37 6 2·9 ng/ml) than matched normal subjects (9·37 6 5·2 ng/ml), the differences were not significant (P<0·05). Furthermore, the physiologically positive BMI/ leptinaemia relationship, consistently found in normal and obese subjects, disappeared in thalassaemic males and was present, but lacked statistical significance in females (Fig 1). Therefore the adipocytes of thalassaemic patients seem unable to maintain adequate leptin production. The lack of any association between circulating leptin and body fat has already been observed in elderly subjects (Moller et al, 1998). Iron deposition studies in animal models have demonstrated that, although absent in the dermis, iron is well represented in subcutaneous layer adipocytes and that iron ions can seriously inhibit adipocyte activity (Youson & Sargent, 1984; Rejholcova et al, 1988). The differences between genders cannot be explained by an unequal iron overload (males, ferritin mean: 2·200 6 0·945 mg/l; females, ferritin mean: 1·938 6 0·848 mg/l; P <0·1), but could be the consequence of the physiologically different extension of the target organ (i.e. more subcutaneous adipose tissue in women). These results suggest that adipose tissue dysfunction can be considered as one of the endocrinopathies affecting thalassaemic patients. The consequent low leptin levels might play a role in the neuroendocrine dysfunctions reported in these patients.

Nutrition in Juvenile Rheumatoid Arthritis

Juvenile Rheumatoid Arthritis (JRA) is one of the more common chronic diseases affecting about one child every 1000 (1). The diagnosis of JRA is established entirely on clinical grounds. Laboratory investigations are rarely pathognomonic and are used instead to assist in the differential diagnosis, detect complications and monitor disease activity. The diagnosis of JRA is based on three criteria: 1) arthritis persisting for more than three months; 2) onset of arthritis before age 16; 3) exclusion of other diseases that may cause arthritis (2). There are three main clinical patterns of the disease: pauciarticular onset which affects up to four joints, polyarticular onset affecting five or more joints, and systemic onset which has prominent extra-articular features such as fever or rash. The pauciarticular JRA carries the greatest risk for iritis. The articular prognosis for these patients is good although a third of them will go on to develop polyarthritis that is difficult to manage. Patients with polyarticular onset have a poorer articular prognosis: 30-50% develop bony erosions and active arthritis that persists into adulthood. Life threatening complications such as pericarditis and amyloidosis are associated with systemic onset JRA. About a third of systemic onset patients develop severe polyarthritis resistant to treatment, and the articular outlook for these patients is poor (3). Ten years after disease onset, 75% of systemic, 50% of polyarticular and 60% of pauciarticular patients have functional limitations (4).