Mutsumi Murakami

Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo

The School Health Law of Japan was passed in 1974 mandating urine screening of elementary and junior high-school students for the detection of renal disease. A first morning urine was obtained on an annual basis for each individual student for the time period 1974–1986. The prevalence of proteinuria and haematuria among elementary school children was 0.08% and 0.54%, respectively, while junior high-school students demonstrated corresponding prevalences of 0.37% and 0.94%. The theoretical merits of this screening programme include the detection of glomerulonephritis with possible early therapeutic intervention. However, a limitation to this approach is its over-sensitivity where asymptomatic urine abnormalities is found to be 10 times greater in frequency than glomerulonephritis histologically.

Ultrasound screening for renal and urinary tract anomalies in healthy infants

Background : Nearly 30% of childhood cases of chronic renal failure in Japan are attributed to congenital anomalies of the kidney and urinary tract (CAKUT), and the number is increasing. Urine screening at school facilitates early diagnosis and treatment of glomerulonephritis, but early screening for anomalies is currently not in practice. The authors evaluated the value of early abdominal ultrasonography screening in 1‐month‐old infants.

Role of Bone Marrow Cells in the Healing Process of Mouse Experimental Glomerulonephritis

Recent studies have shown bone marrow (BM) cells to differentiate into a variety of cell types and to thereby participate in the reconstitution of damaged organs. In the present study, we examined the extent to which BM-derived cells are incorporated into glomeruli during recovery from experimentally induced nephritis. To investigate the localization of BM cells in glomeruli, chimeric mice were prepared by transplanting BM cells from green fluorescent protein (GFP) transgenic mice into wild-type mice. Five weeks later, glomerulonephritis was induced by intravenous injection of Habu snake venom. Groups of mice were then killed every few days for 42 d, and harvested kidney samples were subjected to immunohistochemical and immunoelectron microscopic analyses with the aim of detecting the presence of GFP(+) cells within glomeruli. Chimeric animals injected with Habu venom developed proliferative glomerulonephritis within 1–3 d. The lesion gradually subsided and the glomerular structure returned to normal within 42 d. Consistent with the disease course, large numbers of GFP(+) cells were present within glomeruli on d 1–3, but most had disappeared by d 7. Nevertheless, some GFP(+) cells did remain within glomeruli showing mesangial proliferative changes, and were found to express thrombomodulin (TM), a specific endothelial cell marker. These GFP-TM–double-positive cells accounted for a mean of 1.31–2.24% of the total glomerular nuclei from d 7 through d 42, levels that remained stable for at least 12 mo. It thus appears that BM cells can give rise to endothelial cells that participate in the remodeling of glomeruli.

Mass screening for early detection of congenital kidney and urinary tract abnormalities in infancy

Abstract Background: Recent widespread use of ultrasound has led to new efforts at screening for congenital kidney and urinary tract abnormalities. However, a standard screening methodology, criteria defining abnormalities, and follow‐up procedures remain to be established. In order to establish screening criteria for these abnormalities, we performed a preliminary study in 800 1‐month‐old infants using provisional methods and criteria.

Screening for Proteinuria in Japanese Schoolchildren: a New Approach

Abstract By governmental mandate, Japanese school children are screened annually for proteinuria, hematuria, and glucosuria to identify children with possible renal disorders. We added urine dipstick tests for albumin and creatinine to the Japanese screening protocol, and used their dipstick results for blood, glucose and protein. The sulfosalicylic acid precipitation test was used to confirm “trace” positive protein dipsticks. The Japanese and our screening protocol have in common the same data for glucosuria and proteinuria. Their scheme has an algorithm for repeat testing of children with abnormal results, and further testing and medical evaluation for those showing persistently abnormal values. Out of the 23,121 students, we found seven with likely nephritis, one with confirmed nephritis, one with nephrotic syndrome, 170 with persistent unexplained hematuria, 19 with persistent unexplained proteinuria, 14 cases of urinary tract infection, and 20 cases of likely diabetes mellitus. We conclude that dipstick testing for albumin, protein, creatinine, glucose and occult blood has significant value in a multilevel testing scheme for identifying children with urinary tract abnormalities or diabetes. The assay of albumin increases the sensitivity of the screening, and dividing the albumin by the creatinine concentration reduces the potential errors arising from concentrated or dilute urines.

Autoimmunity in chronic fatigue syndrome in children

We have reported that about half of children with chronic non-specific complaints were positive for antinuclear antibodies (ANA) and that the commonest complaint was fatigue in ANA-positive patients. Therefore, we have proposed a novel disease entity of autoimmune fatigue syndrome (AIFS). In order to investigate the relationship between AIFS and chronic fatigue syndrome (CFS) in children, all CFS patients seen in our clinic were immunologically assessed. Immunological examinations including ANA, autoantibody analysis by Western immunoblotting, lymphocyte subsets and NK activities were performed on 14 CFS patients. Clinical courses of these patients were reviewed retrospectively. None of the patients had fulfilled the CDC criteria for CFS at their first visit. They fulfilled the criteria in a relatively short time, with a 6 months to 6 years smoldering period. All patients had been diagnosed as school refusal by physicians or school teachers. Thirteen patients were positive for ANA and the other one was positive for rheumatoid factor. Twelve patients were positive for antibodies to the 62 kDa protein (anti-Sa) which had been detected in about 40% of AIFS patients. NK activity was not as low as reported in adult patients with CFS. Most of the children with CFS were positive for ANA, suggesting an autoimmune mechanism may play an important role in the pathogenesis of childhood CFS. AIFS patients should be carefully followed because of the possibility of later development of CFS.

Screening for proteinuria and hematuria in school children--methods and results.

In Japan, a urinalysis method in which the first morning urine sample is examined twice (Tokyo method) is currently widespread in the urine screening of school children Mass screening of elementary school and junior high school children for urinary abnormalities using this method yielded a positive prevalence of proteinuria, hematuria and both abnormalities of approximately 0.08%, 0.5% and 0.03%, respectively, for elementary school children and corresponding values of approximately 0.4%, 0.9% and 0.08%, respectively, for junior high school students. These prevalence values may vary depending upon conditions of urine collection, conditions of preservation and transport of urine samples, time interval between collection and testing, testing facility, reagent strips and criteria for evaluation of test results. Since attempts at detection of renal disease through examination of urine tend to yield excess positive rates with an abundance of false‐positives and false‐negatives, the reliability of such testing is reduced unless it is performed correctly under strictly controlled conditions. In order to overcome these difficulties it is mandatory that the entire urinalysis system has a high degree of accuracy.

Epidemiology of school urinary screening over a 30 year period in Tokyo.

Background: A school urinary screening (SUS) system has been conducted for 30 years in Japan, but the cross‐sectional data have never been reported or analyzed. The purpose of the present study was to analyze the data epidemiologically.

Immunogenetic Background of Patients with Autoimmune Fatigue Syndrome

We have previously reported that approximately 50% of children with chronic nonspecific complaints were positive for antinuclear antibodies (ANA), and that a novel autoantibody to a 62kD protein (anti-Sa) was found in 40% of these ANA-positive patients. Therefore, we proposed a distinct disease entity termed autoimmune fatigue syndrome (AIFS). We hypothesized that if autoimmune mechanisms did play an important role in the pathogenesis of AIFS, it is possible that it is immunogenetically regulated as observed in other autoimmune disorders. In order to examine the immunogenetic background of AIFS patients, HLA-A, -B, -C, and -DR loci were analyzed serologically in 61 AIFS patients. AIFS was found to be positively associated with the class I antigen HLA-B61 and with the class II antigen HLA-DR9, with odds ratios of 2.77 (p = 0.015, Pcorr = 0.48) and 2.60 (p= 0.012, Pcorr = 0.17), respectively. A negative association was also found between AIFS and HLA-DR2 with odds ratio of 0.25 (p = 0.029, Pcorr = 0.041). When comparing anti-Sa positive AIFS patients with healthy controls, the odds ratios associated with HLA-B61, DR9, and DR2 were 3.42 (p = 0.021, Pcorr = 0.22), 3.96 (p = 0.0011, Pcorr= 0.015), and 0.16 (p = 0.0022, Pcorr= 0.031), respectively. Thus, the HLA associations observed in this study suggested that immunogenetic background might play a role in AIFS

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

Individual animals in the closed colony population of ddY mice were analyzed to clarify the major cause of age-dependent elevation of serum IgA and the appearance of human IgA nephropathy (IgAN)-like symptoms. Based on the serum IgA levels, the mice were classified into two subgroups. One was a high serum IgA group with some manifestations of IgAN through aging (ddYHigh), and the other was a normal serum IgA group without IgAN (ddYNorm). The ratio of urinary IgA to serum IgA was significantly reduced in ddYHigh mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddYHigh mice was found to be slower than that in ddYNorm mice. Furthermore, we found that the polymeric Ig receptors (pIgRs) that mediate transcytosis of IgA were poorly expressed in the glomeruli as well as in the intestine of ddYHigh mice, whereas the pIgRs were more abundantly expressed in ddYNorm mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddYHigh population. Taken together, these results suggest that a systemic defect in pIgR expression may result in impaired IgA secretion and accumulation of IgA in the serum of ddYHigh mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddYHigh mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.