Background: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) have many pathological and immunological features in common, and it has been suggested that these two diseases are clinical variants of the same disease process. However, since Henoch-Schonlein purpura (HSP) is a systemic vasculitis, often preceded by upper respiratory infections, it is suggested that HSP is caused by more prominent antigenic stimulations than that of IgAN. We previously reported that the glomerular infiltrating CD8 positive cells and the glomerular expression of α-smooth muscle actin (α-SMA) were the predictors of disease progression of IgAN. The aim of this study is to determine whether the renal infiltration of CD8 positive cells, and the expression of α-SMA and transforming growth factor-β (TGP-β) are similar between in HSPN and in IgAN.
  Methods: Twenty-six children including 6 patients with HSPN and 20 patients with IgAN enrolled in this study. We assessed glomerular and interstitial infiltration of CD8 positive cells and the expression of α-SMA and TGF-β using an indirect immunofluorescent method on the renal tissues of the biopsy materials. We analyzed their relation with the degree of proteinuria and renal histological changes in HSPN, and compared them between in HSPN and in IgAN.
  Results: In HSPN, the degree of interstitial infiltration of CD8 positive cells was correlated with urinary protein (p=0.0458). There were no correlations for the infiltration of the glomerular CD8 cells, and the expression of α-SMA and TGF-β with urinary protein and histological findings. In comparison between HSPN and IgAN, there were no significant differences of clinical and laboratory findings except for age (HSPN<IgAN, p=0.0056). The number of glomerular CD8 positive cells was significantly higher in HSPN than in IgAN (p=0.0051). The renal expression of α-SMA and TGF-β were similar between in HSPN and in IgAN.
  Conclusions: These results suggest that antigenic stimulations, which could promote the infiltration of CD8 positive cells into the glomeruli, affect more prominently the patients with HSPN than those with IgAN.

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  The mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown. We have demonstrated that IgA1 is capable of binding carboxy(C)-terminal fibronectin fragment, which is one of the essential parts for exogenous fibronectin to incorporate into the extracellular matrix (J Am Soc Nephro1, 10: 256-63, 1999). Therefore, we investigated the complex of IgA1 and the fibronectin fragment, which may contribute to the deposition of IgA1 through fibronectin. The mixture of IgA1 and cathepsin D-digested fibronectin fragments was reacted with confluent cell layers of cultured human fibroblasts or mesangial cells for 3 hr, and was removed. Cells were cultured with medium for an additional 24 hr, and were fixed by periodate-lysine-paraformaldehyde for the immunofluorescence with FITC-labeled anti-human IgA. The coarse and punctate clusters of IgA1 staining was obtained both on fibroblasts and mesangial cells, and the pattern was similar to that seen in IgA nephropathy. Cathepsin D-digested fibronectin fragments were further separated using heparin- or gelatin-affinity chromatography. The mixture of IgA and heparin-binding fractions or flow-through material from gelatin chromatography was shown to be responsible for the IgA staining. The mixture of IgA and gelatin-binding fractions or flow-through material from heparin-affinity chromatography did not attribute to the IgA staining. Western blot analysis using anti-FN antibodies revealed that these fractions contained C-terminal 43kDa and amino-terminal fibronectin fragments, the latter of which is also known as the other essential part for assembling exogenous fibronectin into the matrix. These results suggest that the complex of IgA1 and fibronectin fragments might contribute to the deposition of IgA1 to extracellular matrix through the mechanism of assembly of exogenous fibronectin into extracellular matrix in IgA nephropathy.

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  Regular ultrasonic examination of the abdomen has been performed on a total of 98 patients suffering from either of seven diseases most likely to be complicated by Wilms' tumor, i. e., Beckwith-Wiedemann syndrome, hemihypertrophy, Sotos syndrome, von Recklinghausen disease, congenital aniridia, Denys-Drash syndrome, and horseshoe kidney at our three hospitals, with the aim of making early detection of Wilms' tumor. The patients were aged from 0.2 to 20.0 years with the median age of 4.2 years at the final examination. Wilms' tumor, hepatoblastoma and mixed hamartoma of the liver occurred each in one infant patient (aged from 0.5 to 1.3 years) during the progress observation period ranging from 0.2 to 13.5 years (median period; 5.9 years).
  These findings indicated that an evaluation of not only the kidneys but also the liver is required for patients in the above disease groups and frequent examination is needed for infants. The prevalence of tumors classified by age for each disease should be clarified by nation-wide survey, and a further reasonable examination method should be established for the early detection of tumors.

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  Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by hepatic glycogen accumulation and renal Fanconi syndrome first described in 1949. Patients of this disorder also have impaired galactose metabolism and are sometimes discovered by their high serum galactose level by means of Guthrie test during newborn screening. The gene responsible for this disorder was identified and three homozygous mutations were found in the GLUT2 gene, a facilitative glucose transporter, all of which predicted truncated translation products. The primary structure of GLUT2 was determined and it consisted of 524 amino acids. The GLUT2 gene is mapped in chromosome 3, q26.1-26.3 and has 11 exons spanning approximately 30 kb. This protein has been studied and speculated to be one of the candidate proteins for non-insulin dependent diabetes mellitus (NIDDM). Although one missense mutation (V197I) was reported in a NIDDM patient, GLUT2 may not play an important role in the development of IDDM in humans.
  Molecular analyses have been performed for FBS patients and reported several mutations. Most mutations are homozygous. The first mutation analyses by Santer et al. reported two nonsense mutations and one frame shift mutation all of which predicted truncated translation products that could not be expected to have functional transporter activity.
  Akagi et al. analyzed two Japanese patients with FBS. No mutation in the entire coding region was detected in one patient. Another patient had a novel homozygous nonsense mutation (W420X). Sanjad et al. reported a family with FBS associated with phosphorylase b kinase deficiency. However the coding sequence of all three Phk subunits genes were all normal and they identified a homozygous missense mutation (P417L) in GLUT2 gene.
  We have analyzed two Japanese patients with FBS. Compound heterozygous mutations (R365X and W444A) were found in one patient with the W444A mutation being the second missense mutation. The other patient had a novel homozygous nonsense mutation (R53X). Both R365X and R53X nonsesnse mutations seem to produce non-functional truncated GLUT2 protein. Trp at amino acid position 444 resides in 11th membrane spanning region. This glucose transporter region is highly homologous. Especially Trp at 444 is conserved in all glucose transporters through 1 to 5. A missense mutation changing Trp at 412 of the GLUT1 severely impairs glucose transport by modulating the inward-facing binding site. Trp at 412 of the GLUT1 corresponds to Trp at 444 of the GLUT2. Taken together it is reasonable to think that Trp at 444 is an important amino acid for functioning glucose transporter activity.
  Mutations in the GLUT2 gene in FBS appear to be heterogeneous. Accumulations of mutations may help in the understanding of the functional domains of the GLUT2.

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  Hemorrhagic cystitis (HC) in patients who have undergone allogeneic bone marrow transplantation (BMT). We have analyzed its incidence, risk factors and clinical findings in 64 children undergoing BMT. HC occurred in 17 patients (26.6%). The median day for onset was day 35 and only 3 patients developed early onset HC. The duration of HC was between 5 and 180 days. Three patients developed severe HC requiring surgicai drainage. The average age of patients with HC was higher than that without HC, however neither underlying diseases nor the severity of the GVHD was significantly associated with frequency of HC. Adenovirus was isolated from three patients, whose symptoms persisted for a long time. One of three developed interstitial nephritis and chronic renal failure. Cyclophosphamide (CY)- induced HC occurred in only 3 patients, who developed HC within two weeks after starting CY. The use of melphalan (Mel) as a conditioning agent was significantly associated with higher rates of HC (13/17). We suggest that the conditioning regimen containing Mel leads to HC after BMT, and this may be explained the higher incidence of moderate to severe mucositis observed following Mel.

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  A l5-year-old Japanese boy developed acute renal failure (ARF) following physical exercise (400-m relay) at school. He developed abdominal pain with nausea and vomiting, which lasted for 3 days from onset, and eyelid swelling was observed 2 days before visiting the hospital.
  He was found to have hypertension (154/90mmHg), blood urea nitrogen of 39.9mg/dl and serum creatinine of 5.3mg/dl, but serum uric acid level was normal (4.3mg/dl), and he was non-oliguric (2,000ml/day). Proteinuria and hematuria were negative. Nausea, vomiting and abdominal pain resolved spontaneously. With a conservative therapy, nonoliguric acute renal failure improved. With recovery of renal function, hypouricemia (0.6mg/dl) became evident. Pyrazinamide and benzbromarone test, i. e. Fractional excretion of uric acid (FEua), was markedly increased (37.7%). FEua in pyrazinamide test was slightly decreased. FEua in benzbromarone test was slightly increased. Results showed that the patient had a defective presecretory uric acid reabsorption. His father was also found to be hypouricemic (1.0mg/dl). Uric acid is a strong antioxidant, and therefore patients with renal hypouricemia are prone to develop acute renal failure. lt is proposed that oral supplementation of antioxidants or scavengers, such as vitamin E, vitamin C, allopurinol, prevent the recurrence of ARF.

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Background
Hematuria is an important finding, because it can be a clue to the diagnosis of glomerular or urological disorders. Quantitative evaluation of hematuria is usually assessed by the number of red blood cells (rbc) under light microscopy (LM), using a centifuged urine sediment. It is, however, postulated that the number of rbc under LM is inaccurate in certain conditions.
Purpose
This study was undertaken to investigate the condition which affects the number of rbc in a centrifuged urine sediment using the LM, and to compare it with the results obtained by a newly developed automated urinary flow cytometer, the UF-100 (Toa Medical Electronics Co., Ltd, Kobe, Japan).
Method & Results
1. Considerable amounts of rbc remained in the supernatant of urine even after routine centrifugation (500g, 5min.). 2. The number of rbc in sediment is affected by the specific gravity of urine, i. e., it was significantly lower in diluted urine than in concentrated urine. 3. Results obtained by the LM correlated well with those by the UF-100. However in several samples, the UF-100 detected the hematuria which was overlooked by the LM.
Conclusion
The number of rbc in a centrifuged urine sediment evaluated by the LM fluctuates considerably by the condition of urine, while an automated urinary flow cytometer, the UF-100 demonstrates rather good reproducibility. From these findings, we suggest that the condition of urine, such as specific gravity, should be taken into consideration when we evaluate the quantity of hematuria analyzed by the LM using centifuged urine samples. In this regard, quantitative analysis by the UF-100 is highly recommended for its good reproducibility.

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  We reported a family with Dent's disease. The 3-year-old boy showed proteinuria (150mg/dl), 49.5% of which comprised low molecular weight protein. Urinary BMG was 37,602μg/l. CCN5 gene of the patient and his mother was analyzed when he was 8 years old. The proband was homozygous for the mutant gene and his mother was heterozygous. At age 10 years he developed nephrocalcinosis and massive proteiuria (2.1g/day). By analyzing urinary protein we detected two other patients in his family, his uncle and his mother's cousin. They had the history of hospital admissiou due to “glomerulonephritis” at age 3 years and 8 years, respectively. They showed mild proteiuria (+) at age 30 years and 34 years, respectively. His ancle showed normal renal function and mild nephrocalcinosis at 38 years.
  These findings suggest that Dent's disease shows diverse phenotypic heterogeneity.

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  We have previously shown that the blood flow analysis of the kidney gave clinically important information on various kidney diseases. In this study we elucidated factors that influence on the kidney blood flow. The difference between Color doppler systems was not significant. The position of patients did not affect significantly on the blood flow. The right and left kidneys gave a statistically same value on the blood flow. The blood flow rate was low in the morning and high in the afternoon. The circadian rhythm suggests the importance of conducting the analysis at a fixed time of a day. The blood flow rate increased after birth, reached at the maximum during infancy, then gradually decreased to the normal adult level. These basic data would be useful to evaluate the result of the kidney blood flow analysis.

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  To determine the usefulness of routine urinary examination, of measuring urinary β₂-microglobulin (β₂M) and N-acetyl-β-D-glucosaminidase (NAG) levels for the screening of urinary tract abnormalities in 3-year-old children, we performed these examinations and ultrasound screening for urinary tract abnormalities simultaneously. Among l185 children of three years of age who performed ultrasound and routine urinary examination, significant urinary tract abnormalities were detected in 14 children (1.2%). There were four cases with hydronephrosis, two with unilateral small kidney, two with duplex kidney, two with malrotation of the kidney, two with simple renal cyst, one with unilateral renal agenesis and one with bilateral vesicoureteral reflux. There were 49 children with asymptomatic hematuria, 20 children with asymptomatic proteinuria and 82 children with asymptomatic leukocyturia. However, no urinary tract abnormalities were detected by the ultrasound examination among these cases. Among 22 children whose urinary β₂M levels were more than 497μg/gCr (mean+2SD), a case with severe bilateral vesicoureteral reflux who needed surgical correction was included. Among 26 children whose urinary NAG levels were more than 12.0 U/gCr (mean+2SD), no urinary tract abnormalities were detected by the ultrasound examination. Nelther routine urinary examination nor measuring urinary NAG levels were found to be useful for the screening of urinary tract abnormalities. However, measuring urinary β₂M levels may be useful in the detection of high grade vesicoureteral reflux.

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  We reported 4- months- old girl who complicated acute glomerulonephritis associated with Kawasaki disease. She demonstrated gross hematuria, proteinuria, oliguria, edema, ascites and hypertension at the 17 th day from the onset. The laboratory data showed elevation of urinary β2-micro-globulin, serum hypoalbuminemia and severe hypocomplementemia. The ultrasonographic findings demonstrated hyperechoic appearance of bilateral kidneys. She was unresponsive to high dose intravenous γ-globulin therapy (400mg/kg/day) in 10 days, and accompanied with pericarditis, bilateral coronary aneurysms, right facial nerve palsy, pneumonia and pleuritis. Gross hematuria disappeared in 2 weeks, and microscopic hematuria and proteinuria showed improvement gradually within 3 months. The hypocomplementemia was normalized completely in 4 weeks. This clinical course is just like that of acute glomerulonephritis with poststreptococcal infection, suggesting that Kawasaki disease, which is one of the immune complex disease, may cause acute glomerulonephritis.
  This case indicated that in severe Kawasaki disease, the consumption of a large amount of immune complexes may be accelerated by high dose intravenous γ-globulin therapy, and subsequent severe hypocomplementemia and immune complex deposition in glomeruli may cause glomerular injury.

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