Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.

Gallbladder pseudopolyp formation following percutaneous liver biopsy.

Following an unsuccessful liver biopsy in a 16-year-old girl in which only bile was obtained, a sonographic (US) study was performed. The findings were those of free fluid just adjacent to the gallbladder as well as a small intraluminal protrusion of the gallbladder wall. The US features of the gallbladder finding were consistent with a polyp. Gallbladder polyps are very rare in children, however, sporadic case reports do exist. An US study 24 h after the invasive procedure revealed complete regression of the free fluid; the gallbladder wall protrusion has disappeared. We suggest that the tip of the biopsy needle had penetrated the gallbladder wall and caused a bile leak. The needle penetration caused elevation of the inner wall layer at the entrance site, which was indistinguishable from the sonographic findings of a gallbladder polyp [1-4]

A fibroepithelial urethral polyp protruding into the base of the bladder: sonographic diagnosis.

A case of congenital urethral polyp in a 10-month-old boy is presented. These rare congenital tumors can lead to urinary retention, hematuria, urinary tract infections, hydronephrosis and hydroureter. Traditionally the diagnosis was based either on voiding cystourethrography or cystoscopy. The sonographic features of these polyps have only been reported in a few cases in the past. This modality is not infrequently the imaging procedure of choice in the work-up of children with signs and symptoms related to the urinary system. In the case presented herein the polyp was demonstrated initially by sonography as a soft tissue mass arising at the base of the urinary bladder. The differential diagnosis of these lesions is presented.

The diagnostic reliability of anti-endomysial antibody in celiac disease: the north Israel experience.

Assessment of anti-endomysial antibody (EMA) for the diagnosis and follow-up of celiac disease (CD) is widely accepted, but its applicability has never been investigated in Israel. We therefore investigated EMA as a diagnostic tool in a pediatric population, residing in the northern part of Israel, with suspected celiac disease. EMA was assessed by an indirect immunofluorescence assay using monkey esophageal sections as a substrate in 22 active CD, 17 non-active CD, and 22 non-CD children. EMA titers were correlated with small bowel mucosal pathology. Sensitivity and specificity of EMA were 100%. EMA levels are diet dependent, increasing on a gluten-containing diet and decreasing with gluten withdrawal after 3-12 months. EMA is a reliable marker for the diagnosis of CD, and reflects gluten intake changes and patients' dietary compliance. In our laboratory, EMA is suitable for the diagnosis and follow-up of CD.

Aminoaciduria as a marker of acute renal transplant rejection--a patient study.

Over 12 months, urine samples were systematically collected from 40 children who underwent renal transplantation for the treatment of end-stage renal disease. Sequential determinations of the excretion of individual amino acids relative to that of creatinine were carried out on 15 subjects. Nine of these (including three who sustained episodes of acute rejection) retained a native kidney in-situ, while in six patients (including three who underwent an episode of acute rejection) both native kidneys had been removed. In both subgroups, the amino acid/creatinine ratios of early morning urine samples were higher shortly before clinical manifestations of acute rejection became evident than in patients who, following renal transplantation, had stable kidney function, chronic graft rejection, or acute tubular necrosis, with one exception: a patient with one native kidney in-situ in whom acute tubular necrosis developed immediately after transplantation. The amino acids showing the greatest increase included Thr, Ser, Gly, and Ala. These values fell dramatically immediately prior to the clinical episode of acute rejection, with Thr, Ala, and Phe showing the most consistent changes. These alterations in urinary amino acid excretion occurred several days before changes in urinary protein excretion or the serum concentrations of urea and creatinine, and may have a role to play in the monitoring of renal transplant recipients.

A family outbreak of hemolytic-uremic syndrome associated with verotoxin-producing Escherichia coli serotype O157:H7.

All five siblings (three boys and two girls, aged 1.5-9 years) in a family developed hemolytic-uremic syndrome associated with verotoxin-producing Escherichia coli O157:H7 at a lakeside vacation cottage during the fall of 1985. All five were hospitalized and made a full recovery. Both parents remained asymptomatic, and neither had evidence of this infection. In four children who were investigated prospectively, free verotoxin was still detectable in the stools for between 3 and 7 weeks. The prodromal diarrheal illness in the children occurred over a 10-day period. The epidemic curve was consistent with a point-source outbreak, but continuous exposure or person-to-person transmission could not be ruled out. The source of the infection was not identified.

Volume regulation in man during neck-out immersion in a medium with high specific gravity (Dead Sea water).

The effect of immersion for 4 h on arterial blood pressure and the rate or urinary sodium excretion was studied in five subjects both in fresh water and in Dead Sea water (specific gravity 1.19) at 34 C. Following 100 min of immersion, mean systolic and diastolic blood pressure decreased (P less than 0.01) in subjects immersed in fresh water, and increased (P less than 0.05) in those immersed in Dead Sea water. While immersion in fresh water led to hypotension, it was associated with an increased natriuresis. In contrast, the hypertensive response to immersion in Dead Sea water was not associated with an increased natriuresis. It is concluded that under the unique conditions of this experiment, urinary excretion of sodium becomes independent of systemic arterial blood pressure, and is presumably governed by neurohumoral influences originating in the baroreceptors of the low pressure system.

The effect of acute extracellular volume expansion on sodium chloride reabsorption in the diluting segment in man.

1. The effect of extracellular volume expansion (ECVE) during water diuresis, and of water diuresis alone, on the formation of free water in man was compared. 2. ECVE reduced free water formation at any given rate of distal delivery compared with water diuresis. Thus, ECVE depresses distal sodium chloride reabsorption. 3. This attenuation of free water formation occurred both when urine flow (V/100 ml glomerular filtration rate) and distal chloride delivery [(Cwater + Ccl)/100 ml glomerular filtration rate] were used as the terms for distal delivery. 4. We suggest that the distal depression of sodium chloride reabsorption after ECVE is robably due to a direct inhibition of distal sodium chloride transport mechanisms, and not to the flooding of the diluting site by the poorly reabsorbable bicarbonate ion.