Kazunari Kaneko

Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic syndrome.

In order to clarify the mechanism of unusual renal tubular dysfunction seen in a child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells. A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular damage characterized by nonoliguric acute renal failure, increased urinary tubular enzymes and defective urine-concentrating capacity. His renal biopsy specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney tissue specimens obtained from patients without HUS served as controls. Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive staining was observed predominantly in renal tubular cells, while the 7 kidney tissue specimens from control patients did not show positive staining. To the best of our knowledge, this is the first case to show Stx binding and apoptotic cell death in renal tubules on biopsy specimens obtained from a child with Stx-mediated HUS. In conclusion, this case suggests that vascular endothelial cells are not the sole nor the consistent target for Stx-mediated cell injury and that significant renal tubular damage other than glomerular damage might occur in some children with Stx-mediated HUS.

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis

Aims: We investigated the effect of n–3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). Methods: We fed Wistar rats a perilla oil-enriched diet containing α-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing α-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. Results: The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB4 and LTC4 from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. Conclusion: These results suggest that n–3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis.

Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux

Abstractu2008u2008We studied the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in 78 patients with primary vesicoureteral reflux (VUR), and examined renal function by dimercaptosuccinate (DMSA) renoscintigraphy and diethylenetriaminepenta-acetic acid (DTPA) renogram in each genotype. Patients were classified into three genotypes according to the ACE gene I/D polymorphisms: 32 in II genotype, 36 in ID, and 10 in DD. The incidence of presumably congenital unilateral small kidneys was high in DD patients (70%). Glomerular filtration rate obtained from DTPA renogram was 120.7±35.7 ml/min (expressed as mean±SD) in II genotype, 111.7±33.3 in ID, and 88.0±18.0 in DD. The total quantitative DMSA tracer uptake of both kidneys was also low in patients with the D allele. This study shows that the D allele of ACE gene is closely related to small congenital kidneys with refluxing ureters in patients with primary VUR, and in accordance with previous reports, this allele is also related to the progression of reflux nephropathy.

Congenital fibromuscular dysplasia involving multivessels in an infant with fatal outcome

We report the unusual case of a 2-month-old boy with systemic fibromuscular dysplasia (FMD). He presented with congenital renovascular hypertension due to stenosis of the right renal artery, and later developed renal infarction on the contralateral side resulting in renal failure. The boy subsequently died of intracranial haemorrhage at the age of 14 months. During the course, hemiconvulsion caused by a Moyamoya disease-like vascular lesion was noted. Stenotic lesions of both the abdominal aorta and its branches were also revealed by angiography. Post-mortem examination confirmed that the coronary, splenic and mesenteric arteries were also affected and their histological findings were compatible with FMD. To our knowledge, this is the first congenital case of FMD demonstrating a rapidly progressive course resulting in a fatal outcome. In this case, multivessels in both intracranial and extracranial arteries were involved. Conclusion:our case suggests that the nature of fibromuscular dysplasia is congenital in origin and its aetiology, at least in some cases, is a systemic abnormality of vascular development.

Progressive vascular lesions in Williams-Beuren syndrome

SummaryWe report two patients with Williams-Beuren syndrome. The first patient showed no evidence of coarctation of the aorta at the first examination. Seven years later, she developed coarctation of the aorta. In the second patient, we found the progression of renal artery stenosis by serial angiography. We report that vascular lesions may be progressive in Williams-Beuren syndrome.

Cytokines in the gastric mucosa of children with Helicobacter pylori infection

Aim: Few studies have looked at the cytokine profile in gastric mucosa in children with Helicobacter pylori infection. This study investigated cytokines and their effects on histological abnormalities in the gastric mucosa of children with H. pylori infection. Methods: The levels of interferon‐γ (IFN‐γ), interleukin‐4 (IL‐4) and IL‐8 proteins were measured in biopsy specimens from the gastric antrum and corpus of children with H. pylori infection, and related to inflammatory cell infiltrations. Results: The antral and corporal mucosal levels of IFN‐γ and IL‐8 proteins were significantly higher in children with H. pylori infection than in uninfected children, but there was no such difference in the levels of IL‐4 protein. The antral mucosal level of IL‐8 protein was significantly higher than the corporal mucosal level of IL‐8 protein in the infected children. Inflammatory cell infiltration was significantly higher in the infected children than in the uninfected children, but there were no significant correlations between mucosal cytokine levels and inflammatory cell infiltrations.

Acute renal failure due to obstructive uric acid stones associated with rotavirus gastroenteritis

Sirs, The prevalence of urolithiasis in Japanese children is very low [1, 2]. Uric acid is rather uncommon as a constituent of childhood urolithiasis: uric acid stones occasionally develop in conditions associated with excessive production of uric acid, such as tumor lysis syndrome or lymphoproliferative/myeloproliferative disorders. Rare inborn errors of uric acid metabolism, i.e., complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme activity, named LeschNyhan syndrome and Kelley-Seegmiller syndrome, respectively [3, 4, 5], may be complicated by uric acid stones. We describe the first case of a previously healthy child with acute renal failure caused by obstructive uric acid stones of the bilateral pelviureteric junctions associated with rotavirus gastroenteritis. A 13-month boy with an 8-day history of vomiting, watery diarrhea, and low-grade fever was initially admitted to a local hospital because of dehydration. On the following day, he was referred to our hospital as he demonstrated prolonged oliguria despite sufficient fluid replacement therapy. He had been previously healthy with no prior medical problems. There was no familial history of renal disease, including urolithiasis. On admission, physical examination revealed mild edema, a blood pressure of 112/96 mmHg, a pulse of 150 beats per minute, a respiratory rate of 96 per minute, and a temperature of 37.8 C. His body weight was 10 kg, which is average for his age. Laboratory investigations were as follows: white blood cell count 19,100/ml, hemoglobin 10.4 g/dl, hematocrit 30.2%, platelets 425,000/ml, blood urea nitrogen 42 mg/ dl, serum creatinine 2.34 mg/dl, uric acid 14.2 mg/dl, sodium 129 mmol/l, potassium 5.3 mmol/l, chloride 97 mmol/l, calcium 8.5 mg/dl, phosphate 5.6 mg/dl, and C-reactive protein 4.04 mg/dl (normal <0.05). Urinalysis by dipstick showed hematuria (occult blood 3+), proteinuria (1+), and leukocyturia (2+). Urine pH and specific gravity were 5.0 and 1.017, respectively. Uric acid excretion per deciliter creatinine clearance for spot morning urine specimens was high (0.70, normal 0.32€0.11 mg/dl) [6]. Rotavirus antigen in the stool was positive. Ultrasound scan of the kidney in the emergency room showed bilateral dilated pelves, although an obstructive lesion could not be identified. Based on these findings, a presumptive diagnosis of acute renal failure resulting from sustained hypovolemia associated with rotavirus gastroenteritis was made. He was treated with continuous venovenous hemodialysis because of hyperkalemia and hypertension refractory to intravenous fluid replacement and diuretics. On the 2nd hospital day, ultrasound scan of the urinary tract was carefully performed again because of prolonged oliguria. Stone-like masses located at bilateral pelviureteric junctions caused severe obstruction resulting in bilateral hydronephrosis. Abdominal computed tomography confirmed this finding. Therefore, percutaneous nephrostomy tubes were inserted bilaterally under ultrasound guidance on the same day. Soon after placement of the nephrostomy tubes, large amount of urine flowed via the tubes and serum levels of creatinine and uric acid returned to normal within several days. Sandy stones excreted through the nephrostomy tubes with urine proved to be S. Fujinaga ()) · Y. Ohtomo · M. Takada Division of Nephrology, Saitama Children’s Medical Center, Japan e-mail: f_shuich@d2.dion.ne.jp Tel.: +81-48-7581811 Fax: +81-48-7581818

Nephrotic syndrome associated with human parvovirus B19 infection

Abstract.A previously healthy 8-year-old Japanese boy developed nephrotic syndrome during the course of erythema infectiosum due to human parvovirus B19 (PVB19) infection. A renal biopsy showed mesangiocapillary proliferative glomerulonephritis with immune complex deposits associated with PVB19 virus. His renal involvement improved spontaneously.

Nutcracker phenomenon demonstrated by three-dimensional computed tomography.

Abstract. We report a 15-year-old girl with nutcracker syndrome (NCP) in whom three-dimensional helical computed tomography (3D helical CT) was useful for diagnosis; angiographic imaging using 3D helical CT provided fine outlines of the vascular structures in NCP, i.e., a compression of the left renal vein between the aorta and the superior mesenteric artery and the abnormal acute angle between them. Thus, a 3D helical CT enables precise depiction of the anatomical characteristics of renal vasculature and, therefore, may be a useful alternative imaging technique instead of conventional examinations, such as invasive venography or digital subtraction angiography. Further study in a large number of children with vascular abnormalities would be worthwhile.

Extremely high prevalence of hypercalciuria in children living in the Aral Sea region

The Aral Sea region is a natural area seriously polluted by human activities. In addition to the increased prevalence of diverse chronic diseases in children, the risk of developing urolithiasis is reported to be high in this region. This study was undertaken to clarify the prevalence of hypercalciuria in children of the Aral Sea region. A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were screened for hypercalciuria. Urinary sodium excretion (sodium per creatinine, uNa/Cr) in addition to calcium excretion (calcium per creatinine, uCa/Cr) was also calculated for each subject. Mean uCa/Cr (mmol/mmol) and uNa/Cr (mmol/mmol) excretions were significantly higher in Kazalinsk than in Zhanakorgan (uCa/Cr: 0.75 ± 0.74 and 0.33 ± 0.30; uNa/Cr: 3.54 ± 2.27 and 2.89 ± 1.69, respectively, mean ± SD, p < 0.01). Hypercalciuria regarded as an uCa/Cr of more than 0.703 was observed in 79 out of 205 Kazalinsk children (38.6%) while this was seen in only 24 out of 187 Zhanakorgan children (12.8%). Linear regression analysis revealed a direct positive correlation between urinary calcium and sodium excretion (p < 0.01) in Kazalinsk children.