The CC16 A38G polymorphism is associated with the development of asthma in children with allergic rhinitis.

BACKGROUND: Although asthma and allergic rhinitis (AR) are considered to be one syndrome, many questions remain unanswered. Why do some AR patients develop asthma but others do not, and which factors play a role in the development of asthma that have so far not been clearly elucidated. OBJECTIVE: We hypothesize that children with AR who have the Clara cell secretory protein (CC16, secretoglobin 1A1) 38A/38A genotype (rs3741240) have an increased likelihood of developing asthma. METHODS: The study sample included 117 children, with AR, but no asthma diagnosed within the following 5 years, as the control group. Cases group (n=202) included age- and gender-matched children with AR first, and asthma developed 3-5 years later, as the study group. The CC16 genotype was determined by PCR and Sau96I restriction digestion of PCR products. The serum CC16 levels were measured by ELISA. Total serum IgE, allergen specific IgE, eosinophil count and pulmonary function were also measured. RESULTS: In children with rhinitis who develop asthma, the frequencies of the AA genotype were significantly higher than those who did not develop asthma [odds ratio (OR)=2.527; 95% confidence interval (CI)=1.571-4.065; P<0.01]. Serum CC16 levels in the children with rhinitis who develop asthma and carry the AA genotype were significantly lower than those who carry the non-AA genotype and those who did not develop asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that CC16 38A/38A genotype plays a role in the development of early asthma in children with AR. Early identification of rhinitis children at risk may assist in designing preventative approach to asthma development.

Lung abscess in congenital cystic adenomatoid malformation: report of one case.

Congenital cystic adenomatoid malformation (CCAM) of the lung is an uncommon anomaly of fetal development of terminal respiratory structures. Patients with CCAM may present either in the newborn with progressive respiratory distress, or in older children with recurrent pulmonary infections. Lung abscess is an extremely rare presentation. Herein we report an 8-year-old girl with type 1 CCAM who presented as lung abscess.

Minimal change nephrotic syndrome in children with intrauterine growth retardation.

It has been well established that intrauterine growth retardation (IUGR) is associated with greater morbidity and mortality rates during perinatal and adult life. The aim of this study is to clarify whether IUGR, defined as a birth weight less than the 10th percentile for gestational age, influences the clinical course of minimal change nephrotic syndrome (MCNS) in children. The study included 50 children aged 1 to 13 years at the onset of MCNS. The diagnosis of MCNS was confirmed by renal biopsy in 25 children (50%). Eight children (16%) had IUGR at birth. Comparisons between children with and without IUGR showed significant differences in mean number of relapses (13.0 +/- 3.5 versus 3.4 +/- 3.0 relapses; P < 0.0001) and relapse rates (relapses per year, 1.6 +/- 0.3 versus 0.5 +/- 0.4; P < 0.0001). We also observed a greater incidence of steroid dependence (100% versus 21.4%; P < 0.001) in children with than without IUGR. In addition, children with IUGR underwent treatment with cytotoxic agents and cyclosporine more frequently than those without IUGR. There was a significantly greater incidence of complications and concomitant diseases of nephrotic syndrome in children with IUGR; results show that MCNS in children with IUGR had a more unfavorable course and outcome. It is important for clinicians to be aware that IUGR may help in the early identification of children at greater risk for frequent relapses and the development of steroid dependence and/or steroid resistance. More aggressive therapy may be indicated for these children.

46,XY gonadal dysgenesis associated with congenital nephrotic syndrome and sepsis.

The occurrence of nephrosis in the first 3 months of life is rare and is termed 'congenital nephrotic syndrome.' The congenital nephrotic syndrome is a group of heterogeneous diseases with a clinical course that differs markedly from the childhood nephrotic syndrome. The coexistence of a congenital nephrotic syndrome and gonadal dysgenesis in a 46,XY karyotype with normal female external genitalia is extremely rare. Frequent severe infections are often seen in the Finnish type, but sepsis leading to death is rare in the neonatal onset of gonadal dysgenesis. This report describes an unusual case of complete XY gonadal dysgenesis in a 46,XY female neonate with the congenital nephrotic syndrome and overwhelming sepsis.

Allergic diseases in preschool children in Taichung City.

The occurrence of allergic diseases in preschool children was studied on the basis of a questionnaire sent to the parents of 5,408 kindergarten students, 3 to 6 years of age, in Taichung City. The overall response rate was 81% and included 2311 (52.8%) boys and 2062 (47.2%) girls. Allergic diseases had been recognized in 34.6% of the children. The cumulative (lifetime) prevalence of bronchial asthma (BA), allergic rhinitis (AR), atopic eczema (AE), and urticaria were 9.4%, 26.4%, 6.6% and 6.8%, respectively. The current (past 12 months) prevalence of BA, AR, and AE was 6.7%, 14.8%, and 3.5%, respectively. BA and AR occurred more frequently in boys than in girls (P < 0.001); no significant difference was found between boys and girls in AE (P = 0.328). There were statistically significant relationships between positive family history and BA, AR and AE (P < 0.001). In conclusion, allergic diseases constitutes an important health problem for pre-school students in Taichung City.

Maturational changes in rabbit renal cortical phospholipase A2 activity.

Several studies have demonstrated that the neonatal kidney has a markedly attenuated response to parathyroid hormone (PTH); however, the cause for this blunted response is unknown. PTH stimulated cAMP production by 215 +/- 18% in neonatal proximal tubule suspensions compared to a 35 +/- 7% increase in adult proximal tubules. Thus, neonatal proximal tubules have functioning PTH receptors and a greater adenylate cyclase response than the adult segment. In adult proximal tubules, PTH stimulates phospholipase A2 (PLA2) activity and the inhibition of Na,K-ATPase activity by PTH is blocked by inhibitors of PLA2. We examined whether maturational changes in renal cortical activity could play a role in the attenuated response to PTH in the neonatal proximal tubule. Compared to adults, neonates had a lower renal cortical cytosolic PLA2 (cPLA2) activity, assessed as the release of 14C-arachidonic acid (AA) from labeled phosphatidyl choline (0.44 +/- 0.10 vs. 0.74 +/- 0.06% 14C-AA released/min/mg protein, P < 0.05) and microsomal PLA2 activity (0.32 +/- 0.03 vs. 1.20 +/- 0.13% 14C-AA released/min/mg protein, P < 0.001). The protein abundance of cPLA2 was not different between the neonatal and adult renal cortex as assessed by immunoblot assay. Thus, the difference in activities must be due to a difference in regulation of cPLA2. Annexin 1 (lipocortin 1) has been shown to inhibit PLA2 activity by binding to phospholipid substrate. Annexin 1 protein abundance was higher in neonatal than in adult renal cortex (P < 0.001). Thus, the lower activity of PLA2 in the neonatal tubules may be due in part to higher expression of annexin 1. PLA2 activation by PTH, -8-bromo-cAMP and PMA was assessed as 3H-AA release from prelabeled suspensions of neonatal and adult proximal tubules. PTH (10(-7) M), 8-bromo-cAMP (10(-4) M) and PMA (5 x 10(-8) M) significantly increased 3H-AA release from adult tubules (P < 0.05) but had no effect on neonatal tubules (P = NS). Thus, PTH, 8-bromo-cAMP and PMA stimulated PLA2 in adult but not neonatal proximal tubules. In conclusion, the maturational changes in renal cortical PLA2 activity may be a factor in the blunted response of neonatal proximal tubules to PTH.

Maturation of rabbit proximal convoluted tubule chloride permeability.

Chloride transport in the rabbit proximal convoluted tubule (PCT) has components of active, transcellular, and passive, paracellular transport. The preferential reabsorption of bicarbonate and organic solutes by the early proximal tubule leaves the luminal fluid with a higher chloride concentration than that in the peritubular capillaries. Previous studies have suggested that solute permeability of the paracellular pathway may be higher in the neonatal PCT and that the neonatal proximal tubule reabsorbs solutes by passive mechanisms to a greater extent than the adult segment. A higher chloride permeability would provide a mechanism for the greater rate of passive NaCl transport by the neonatal proximal tubule. The purpose of the present in vitro microperfusion study was to directly examine the chloride permeability of neonatal and adult PCT. Superficial and juxtamedullary, neonatal and adult PCT were perfused with a high chloride perfusate without organic solutes, simulating late proximal tubular fluid, at 20 degrees C, and bathed in a serum-like albumin solution. Chloride concentrations in the perfusate and the collected fluid were measured by electrometric titration. Neonatal juxtamedullary PCT chloride permeability (PCl) was significantly lower than adult juxtamedullary PCT PCl (0.15 +/- 0.25 x 10(-5) cm/s versus 5.23 +/- 0.57 x 10(-5) cm/s, p < 0.001). The PCl of neonatal superficial PCT was not different from that of adult superficial PCT (0.81 +/- 0.48 x 10(-5) cm/s versus 0.05 +/- 0.62 x 10(-5) cm/s). Thus, there is a maturational increase in juxtamedullary PCT PCl, whereas superficial PCT PCl remains very low. The passive diffusion of chloride in neonatal PCT is extremely low and is not a mechanism to explain a higher rate of passive NaCl transport in this segment.

Decreased urinary epidermal growth factor in children with acute renal failure: epidermal growth factor/creatinine ratio not a reliable parameter for urinary epidermal growth factor excretion.

To verify some animal experimental results in humans, we have studied urinary epidermal growth factor (EGF) excretion in normal children as well as children with acute renal failure (ARF). Urinary EGF excretion was expressed as a ratio of urinary EGF to urinary creatinine concentration (EGF/Cr) for random and 24-h urine, and a daily total urinary EGF for 24-h urine. The highest urinary EGF/Cr in children was found at 1 mo to 3 y of age. There was a highly significant correlation between random urine EGF/Cr and 24-h urine EGF/Cr (r = 0.92, p < 0.001), whereas no correlation of urinary EGF/Cr with daily total urine EGF was found. During the course of ARF, a decline in urinary EGF/Cr from the period before peak serum creatinine to the period after the declination of serum creatinine was noted (p = 0.013, n = 13, by repeated measure analysis), with a constant low daily total urine EGF (p value not significant). However, a rise in both urinary EGF/Cr and daily total urine EGF was found between the period of serum creatinine decline and the period of completely normal serum creatinine (p < 0.001). Serum EGF remained unchanged throughout the course of ARF. These results suggest 1) the possible role of EGF in renal growth or maturation during the first 2 or 3 y of life, 2) the possible renal origin of human urinary EGF, and 3) decreased urinary EGF excretion in children with ARF. In particular, EGF/Cr is not a reliable indicator for the expression of actual urinary EGF excretion in ARF. Instead of urinary EGF/Cr, urinary EGF concentration may be used to predict the daily total urinary EGF excretion during ARF. These results provide the pattern of urinary EGF excretion during ARF in children and may be of help for further clinical studies.

Stimulation of proximal convoluted tubule phosphate transport by epidermal growth factor: signal transduction.

The present study investigated the signal-transduction pathway responsible for the epidermal growth factor (EGF) stimulation of phosphate transport (JPhos) in the rabbit proximal convoluted tubule (PCT). Genistein, 10(-4) M, bath and lumen, an inhibitor of EGF receptor tyrosine kinase activity, blocked the EGF effect on JPhos, consistent with a role for tyrosine kinase in the signal-transduction pathway. Both staurosporine (5 x 10(-8) M) and calphostin C (10(-8) M), inhibitors of protein kinase C, blocked the EGF stimulation of JPhos, indicating that protein kinase C is involved in EGF signaling. Intracellular calcium (Ca2+i) concentrations were measured in perfused tubules using fura PE3 to determine whether changes in Ca2+i were also part of the signaling pathway. After addition of 3 nM EGF, there was no change in Ca2+i, suggesting that stimulation of protein kinase C is not from phosphatidylinositol hydrolysis by phospholipase C-gamma. To determine whether phospholipase A2 (PLA2) is involved, the inhibitor mepacrine was used. Mepacrine (5 x 10(-5) M) had no direct effect on PCT transport but blocked the stimulatory effect of EGF on JPhos. PLA2 activity, assessed as free arachidonic acid release from proximal tubules in suspension, increased by 18.8% with 3 nM EGF. Thus the stimulation of JPhos by EGF is mediated via a signal-transduction pathway involving tyrosine kinase, protein kinase C, and PLA2.

Heterogeneity of chloride/base exchange in rabbit superficial and juxtamedullary proximal convoluted tubules.

Active transcellular NaCl transport in the proximal convoluted tubule (PCT) is via apical parallel Na/H and Cl/base exchange. The mechanism of Cl/base exchange remains unclear. The present in vitro microperfusion study examined the mechanism of Cl/base exchange in superficial and juxtamedullary PCT by examining the rate of change in intracellular pH in response to luminal Cl removal. In superficial PCT the rate of Cl/base exchange was 24.0 +/- 2.3 without formate, 36.4 +/- 6.6 with 10 microM formate (P < 0.05), and 43.6 +/- 2.8 pmol.mm-1.min-1 (P < 0.001) with 1 mM luminal formate. Cl/base exchange was inhibited by luminal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in the presence and absence of formate. In juxtamedullary PCT, Cl/base exchange was 22.2 +/- 3.8 without formate and 25.0 +/- 5.4 pmol.mm-1.min-1 in the presence of 1 mM luminal formate [P = not significant (NS)]. Cl/base exchange was inhibited by luminal DIDS in juxtamedullary PCT. The rates of Cl/base exchange in both superficial and juxtamedullary PCT were not affected by 0.1 mM acetazolamide and 2 mM cyanide and were the same in the presence and absence of HCO3/CO2, consistent with Cl/OH rather than Cl/HCO3 exchange. To examine the effect of formate on PCT transport, tubules were perfused with a high-Cl solution without organics simulating late proximal tubular fluid. In superficial PCT net volume absorption (JV) was 0.00 +/- 0.05 in the absence of formate and 0.14 +/- 0.06 nl.mm-1.min-1 in the presence of 1 mM formate (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal function in neonatal hyperbilirubinemia.

A total of 75 jaundiced infants with gestational ages ranging from 37 to 42 weeks were studied during the first 10 days of age to evaluate renal function by measuring endogenous creatinine clearance (Ccr), fractional excretion of N-acetyl-beta-D-glucosaminidase (NAG) to creatinine, fractional excretion of sodium (FENa) and urine osmolality. All jaundiced infants were divided into two groups. Group 1 infants (n = 35) had total serum bilirubin levels ranging between 21 and 39.6 mg/dl (mean 27.2). Exchange transfusions were performed in all group 1 infants at the time of the initial study. Group 2 infants (n = 40), whose total serum bilirubin levels ranged between 12.3 and 20 mg/dl (mean 16.4), received phototherapy, except for 2. Conjugated bilirubin levels were less than 1.0 mg/dl in all these infants. Results were compared with 25 untreated control infants with corresponding gestational and postnatal ages. Follow-up studies were done in 27 of the 35 group 1 infants and in 32 of the 40 group 2 infants prior to hospital discharge, when total serum bilirubin levels had decreased to less than 10 mg/dl. Ccr, fractional excretion of NAG to creatinine, FENa and urine osmolality of group 1 infants were statistically significantly different when compared to those of group 2 and the control infants. The measured parameters in the post-treatment follow-up study of group 1 infants returned to near-normal levels when total serum bilirubin levels became normal. However, no significant differences were seen between group 2 and the control infants in any of the measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal calcification in very low birth weight infants.

Between January 1990 and December 1991, serial real-time ultrasound examinations and analyses of urine were performed on a total of 50 infants with birth weights less than 1,500 g to assess the incidence of renal calcification. Five infants (10%) developed renal calcification at a mean age of 48.8 +/- 14.1 days. These 5 infants with renal calcification had significantly shorter gestations (28.2 +/- 0.8 vs. 30.1 +/- 1.7 weeks, p < 0.0005) and lower birth weights (934 +/- 45 vs. 1,311 +/- 188 g, p < 0.0005) when compared with infants without renal calcification. None of the affected infants were treated with furosemide. Affected infants had a mean urine volume of 85.8 +/- 11.3 ml/kg/24 h, mean urine calcium level of 5.07 +/- 1.18 mg/kg/24 h, mean urine calcium to creatinine (mg/mg) ratio of 0.67 +/- 0.09, and a mean urine N-acetyl-beta-D-glucosaminidase (NAG) to creatinine (U/g) ratio of 259 +/- 133. Urinalyses showed that affected infants had significantly higher urine pH values and hematuria. Alkaline phosphatase concentrations and initial parathyroid hormone levels were not different among the two groups. In summary, renal calcification occurred in 10% of very low birth weight infants and multiple risk factors seem to be contributory. The smaller, sicker and more immature infants appear to have increased risk for developing renal calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary N-acetyl-beta-glucosaminidase in children with idiopathic nephrotic syndrome.

Twenty-one nephrotic children, aged 2 to 15 years, were studied for their urinary N-acetyl-beta-glucosaminidase (NAG) and daily urinary total protein, in a total of 35 episodes. Among them, 18 patients had urinary NAG levels (77.3 +/- 112.1 u/g Cr) above normal mean + 2 SD for age, while 3 had normal levels during the nephrotic stage. No or poor correlation was found between urinary protein and NAG. In eight of these patients, urinary NAG levels during heavy proteinuria and after remission were evaluated. No significant change was detected. These observations suggest that urinary NAG excretion in nephrotic children is not caused by an increased glomerular permeability to macromolecules. Instead, the elevated urinary NAG may reflect the activity of associated renal tubular dysfunction or tubulointerstitial involvement in the nephrotic syndrome.

Correlation between total urinary protein quantitation and random urine sample protein/creatinine ratio in children.

Random urine samples and 24-hour urine samples were obtained prospectively from 5 healthy children and 28 children with renal diseases, aged 2 to 14 years. The relationship between the random urine protein/creatinine ratio (Up/Ucr) and total daily protein excretion were studied. Protein concentrations were measured using a Coomassie blue binding technique. The Up/Ucr measured in 61 urine samples correlated closely with 24-hour urine protein excretion. In log-transformed data, the correlation was linear with a coefficient of 0.97 (log Up/Ucr mg/mmole = 0.786 + 1.018 logTP, TP in mg/h/M2). The Up/Ucr that coincided with a protein excretion of 4 mg/h/M2 was 25.1 mg/mmole (0.222 mg/mg) and of 40 mg/h/M2 was 261 mg/mmole (2.31 mg/mg). The results of our study indicate that Up/Ucr is an accurate estimate of quantitative protein excretion. In clinical practice this is a suitable method of quantification for proteinuria in patients with renal disease.

Complications of nephrotic syndrome in children.

One hundred and ninety-three nephrotic children with a total of 271 admissions during the past decade, from 1980 to 1989, were retrospectively reviewed for acute complications and unusual features of nephrotic syndrome. One hundred and forty-nine patients were male, 44 female. Hypertension was found in 41 children (21.2%). Nine patients (4.7%) had a total of 11 episodes of hypovolemic shock. These shock patients had a more severe hemoconcentration (mean hemoglobin concentration 19.6 +/- 1.5 g/dl) and hyponatremia (mean serum sodium 127.5 +/- 8.5 mmole/L). Bacterial infections occurred in 28 children (14.5%) with primary peritonitis in 13, sepsis in 6, cellulitis in 4, urinary tract infection in 4 and osteomyelitis in 1. Almost all infections were caused by gram-negative bacilli. Other complications or features included tetany in 4 (2.1%), thromboembolism in 2 (1.0%), pancreatitis in one (0.5%) and Fanconi syndrome in one (0.5%).

Autosomal dominant polycystic kidney disease: an unusual presentation as unilateral renal mass in the infant.

The onset of autosomal dominant polycystic kidney disease in infants and children is unusual, and renal involvement is typically bilateral. The presentation of a unilateral renal mass in such a disorder is extremely rare. We report a 2-month-old infant with autosomal dominant polycystic kidney disease presenting with unilateral renal involvement; the literature concerning this entity is reviewed.

Urinary N-acetyl-beta-glucosaminidase in normal Chinese children and children with pyelonephritis.

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) was measured in random urine as the ratio of NAG to grams of urinary creatinine in 120 normal Chinese children. The results showed that the NAG was elevated in newborn babies and infants, and decreased to adult level after two years of age. Thirteen children with urinary tract infection, who were clinically suggested or proved to have pyelonephritis, were evaluated for their urinary NAG excretion. The level of enzymuria at diagnosis in these patients was significantly higher than that of normal children for age. Eleven longitudinal follow-up data including levels at diagnosis, end of treatment, and two to four weeks after treatment showed that the mean urinary NAG at diagnosis was 109.82 +/- 87.30 u/g creatinine, compared with 75.26 +/- 48.82 u/g creatinine at the end of treatment and 15.37 +/- 9.69 u/g creatinine after recovery. These data suggest the presence of renal tubular cell injury in upper urinary tract infection. Thus urinary NAG may play a role in differentiating lower from upper urinary tract infections.

Focal glomerulosclerosis manifested with nephrotic syndrome.

To assess the long-term outcome for nephrotic children with focal glomerulosclerosis, 23 patients were studied. Twenty were male and three female; the mean age at onset was 7.2 +/- 4.0 years. Twenty of the 23 children had focal segmental glomerulosclerosis, and the other 3 showed focal global sclerosis in renal biopsy specimens. Hypertension (11/23) and hematuria (9/23) were frequent clinical features. Glycosuria (4/23) was occasionally noted. Of the patients studied 13 were initial steroid responders and 10, steroid nonresponders. The mean duration of follow-up for the entire group was 4.7 +/- 4.0 years (ranging from 1 to 13.5 years). From the total study group, 13% had renal deaths; 13% had decreased creatinine clearance, but not end-stage renal disease; 35% had persistent proteinuria; and 39% were in remission. None of the three patients with focal global sclerosis developed chronic renal failure. The data suggest that for children with focal glomerulosclerosis, clinical outcome is not too pessimistic. Except for glycosuria, no clinical or morphologic features were predictive of the development of chronic renal failure, in this study.