Takeshi Matsuyama

Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children.

Objective: The purpose of this study was to evaluate the effects of a catechin‐rich beverage on body fat and cardiovascular disease risk factors in obese children and to verify the safety of its use.

Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease.

Recent linkage analyses of nondiabetic African-American patients with focal segmental glomerulosclerosis (FSGS) have identified MYH9, encoding nonmuscle myosin heavy chain IIA (NMMHC-IIA), as a gene having a critical role in this disease. Abnormalities of the MYH9 locus also underlie rare autosomal dominant diseases such as May-Hegglin anomaly, and Sebastian, Epstein (EPS), and Fechtner (FTNS) syndromes that are characterized by macrothrombocytopenia and cytoplasmic inclusion bodies in granulocytes. Among these diseases, patients with EPS or FTNS develop progressive nephritis and hearing disability. We analyzed clinical features and pathophysiological findings of nine EPS-FTNS patients with MYH9 mutations at the R702 codon hot spot. Most developed proteinuria and/or hematuria in early infancy and had a rapid progression of renal impairment during adolescence. Renal histopathological findings in one patient showed changes compatible with FSGS. The intensity of immunostaining for NMMHC-IIA in podocytes was decreased in this patient compared with control patients. Thus, MYH9 R702 mutations display a strict genotype-phenotype correlation, and lead to the rapid deterioration of podocyte structure. Our results highlight the critical role of NMMHC-IIA in the development of FSGS.

Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children : a multicenter study

BackgroundEnzymatic methods have recently been used to measure creatinine (Cr) instead of the Jaffe method. Therefore, it is necessary to determine the reference serum Cr value for these enzymatic methods to evaluate renal function in Japanese children.MethodsTo determine reference values of serum Cr in Japanese children, 1151 children (517 male, 634 female) aged between 1 month and 18 years had their serum Cr values measured by an enzymatic method. To be included in the study the children had to be without kidney disease, urogenital disease, infectious disease, inflammatory disease, dehydration, muscular disease, anomaly syndrome, cardiovascular disease, malignant disease, hypertension, liver or pancreas disease, or pregnancy.ResultsThe medians of reference values increased gradually with age, i.e., 0.30 mg/dl at 4 years old and 0.41 mg/dl at 10 years old. In adolescence, they increased significantly more rapidly in males than in females. We found a linear regression equation capable of estimating the reference value of serum Cr in children aged 2–11 years, and quintic regression equations capable of estimating the reference values of serum Cr in male and female children of all ages.ConclusionThe reference serum Cr levels determined by an enzymatic method related to age, gender, and body length, and our linear and polynomial equations showing the relationship between body length and serum Cr level will be applicable for screening of renal function in Asian as well as Japanese children.

Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome

BACKGROUND We previously established a treatment protocol for conventional cyclosporine (Sandimmune, Novartis, Basel, Switzerland) in children with frequently relapsing nephrotic syndrome; ∼50% of patients remained relapse free for 2 years, without serious adverse events. Recently, microemulsified cyclosporine (Neoral, Novartis), which has a more stable absorption profile than conventional cyclosporine, has been developed. We tested the hypothesis that microemulsified cyclosporine is at least as effective as conventional cyclosporine. METHODS To evaluate the safety and efficacy of microemulsified cyclosporine, a prospective, multicentre trial was conducted according to the previously established protocol, using microemulsified cyclosporine instead of conventional cyclosporine. The duration of treatment was 24 months. During the first 6 months, patients received microemulsified cyclosporine in a dose that maintained the trough level between 80 and 100 ng/mL of cyclosporine. For the next 18 months, the dose was adjusted to maintain a level between 60 and 80 ng/mL. RESULTS A total of 62 patients (median age, 5.4 years; 48 males, 14 females) were studied. The frequency of relapse decreased from 4.6 ± 1.4 to 0.7 ± 1.5 times per year (P < 0.0001). The probability of relapse-free survival at Month 24 was 58.1% (95% confidence interval, 45.8-70.3%). The probability of progression (to frequently relapsing nephrotic syndrome)-free survival at Month 24 was 88.5% (95% confidence interval, 80.4-96.5%). Cyclosporine nephrotoxicity was detected in only 8.6% of patients who underwent renal biopsy after 2 years of treatment. Antihypertensive agents were administered to 12.9% of the patients to control hypertension without severe sequelae. CONCLUSIONS Microemulsified cyclosporine administered according to our treatment protocol is safe and effective in children with frequently relapsing nephrotic syndrome.

Two-Year Follow-Up of a Prospective Clinical Trial of Cyclosporine for Frequently Relapsing Nephrotic Syndrome in Children

BACKGROUND AND OBJECTIVES Although the safety and efficacy of cyclosporine in children with frequently relapsing nephrotic syndrome (FRNS) have been confirmed, no prospective follow-up data on relapse after cyclosporine have appeared. This study is a prospective follow-up trial after 2-year treatment with cyclosporine to investigate cyclosporine dependency after its discontinuation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Participants who had undergone 2-year protocol treatment with microemulsified cyclosporine for FRNS between January 2000 and December 2005 were followed for an additional 2 years. The primary end point was relapse-free survival after the complete discontinuation of cyclosporine, and the secondary end point was regression-free survival (time to regression to FRNS). RESULTS After exclusion of 7 patients who showed regression to FRNS during the 2-year treatment period, 49 children (median age, 6.5 years) were followed, and classified as children without (n=32; group A) and with (n=17; group B) relapse during the initial cyclosporine treatment. Overall, relapse-free survival probability at 24 months after cyclosporine discontinuation was 15.3% and regression to FRNS-free survival probability was 40.8%. By group, the probability of relapse-free survival was significantly higher in group A (17.9%) than in group B (8.3%) (P<0.001). CONCLUSIONS Children with FRNS who receive cyclosporine are at high risk of relapse after discontinuation, particularly those who experience relapse during cyclosporine treatment.

Reevaluation of glomerular charge selective protein-sieving function

Recently, disorders of the slit diaphragm have been considered as major causes of proteinuria in renal disease and the charge barrier function of the glomerular capillary wall has been given less attention. We evaluated the charge selectivity index (CSI) in 40 patients with podocyte disease (PD), 75 with chronic glomerulonephritis (CGN), and 8 with Dent disease, to reexamine the charge barrier function. We evaluated CSI in Dent disease because the urinary protein profile in Dent disease was assumed to be a concentrate of a normal glomerular filtrate. CSI was defined as the renal clearance ratio between IgA and IgG. CSI values (mean ± SD) in the CGN and PD groups and in Dent disease were 1.12 ± 0.25, 0.42 ± 0.31, and 0.16 ± 0.06, respectively, suggesting that the charge barrier function was defective in the CGN group and of reduced capacity in the PD group. The results suggest that functional interactions between the slit diaphragm and the glomerular basement membrane exist, and that a slit diaphragm disorder is accompanied by a decrease in the charge barrier function in PD, as argued by the conventional hypothesis.

Importance of mechanical damage to urinary red blood cells by the glomerular basement membrane

The reasons for morphological changes of urinary red blood cells (RBC) in patients with glomerulonephritis are still controversial. In order to evaluate the importance of mechanical damage by the glomerular basement membrane (GBM), we examined urinary RBC taken from the patients with two different diseases which have characteristic GBM changes. Urinary RBC taken from 20 patients with Alport syndrome and nine with thin GBM disease were examined using a scanning electron microscope. Nineteen out of the 20 patients (95.0%) with Alport syndrome showed ‘glomerular type’, while five of the nine patients (55.6%) with thin GBM disease showed ‘glomerular type’. These results suggest that more complicated GBM abnormalities cause more severe RBC distortion. Therefore, we conclude that mechanical damage by the GBM may be the major factor in dysmorphism of urinary RBC.