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In Japan, rotavirus (RV) vaccines have already been introduced but not used for universal vaccination as of 2018. Therefore, we identified cases of severe rotavirus gastroenteritis (RVGE) in children younger than three years of age and investigated the occurrence of infection before and after the introduction of RV vaccines. An ecological study through prospective surveillance was conducted in four pediatric clinics in Shibata City, Niigata Prefecture, Japan, during the 2011 to 2018 RVGE epidemic seasons. We divided the study period into three eras: pre-vaccine introduction era (2011), low-mid coverage transitional era (2012 to 2014, RV vaccine coverage rate: 32.9–56.5%), and high coverage plateau era (2015 to 2018, 67.7–81.7%). In this study, the incidence rate of severe RVGE was significantly lower in the plateau era than in the pre-vaccine introduction and transitional eras. Furthermore, the hospitalization rate due to RVGE in Shibata City was lower in the plateau era than in the pre-vaccination introduction and transitional eras. The number of hospitalizations due to RVGE in subjects who required or did not require intravenous rehydration at the pediatric clinics significantly decreased with the increase in vaccine coverage rates by more than 70% in the plateau era.

The impact of rotavirus (RV) vaccination in reducing severe rotavirus gastroenteritis (RVGE) in outpatient settings was prospectively surveyed in three pediatric clinics in Shibata City. In children younger than 3 years of age, the occurrence of severe RVGE among all acute gastroenteritis (AGE) was found to be significantly lower in three seasons after introduction of RV vaccines, compared to that in 2011, before introduction of RV vaccines. The incidence rates of severe RVGE among children younger than 3 years of age were found to be reduced by 71.2%, 47.7%, and 81.1% for 2012, 2013, and 2014, respectively, compared to that in 2011. These results suggest that the RV vaccination is effective for the prevention of severe RVGE in Japanese voluntary RV vaccination settings with estimated coverage rates of 32.5%, 40.5% and 47.1% for 2012, 2013 and 2014, respectively. It is expected that the reducing effect on severe RVGE would be persistently established by increasing the vaccine coverage rates.

The occurrence of severe rotavirus gastroenteritis (RVGE) in children under 3 years of age before and after the introduction of rotavirus vaccine was prospectively surveyed in three pediatric clinics in Shibata City, Niigata Prefecture, Japan, during the 2011 and 2012 RVGE epidemic seasons. In this observational study, a significantly lower occurrence of severe RVGE among severe gastroenteritis cases was observed in 2012. The incidence rate of severe RVGE among outpatients in 2012 was significantly lower than that in 2011. Despite the significant reduction in severe RVGE, the results must be interpreted with caution because the surveillance period is short and requires extension to conclude whether the reduction in the incidence of severe RVGE is a direct effect of rotavirus vaccination. Therefore, we will continue the survey to evaluate the impact of vaccination.

We encountered a 16-year-old boy with Japanese Dent's disease who exhibited renal insufficiency and an osseous disorder of the spine. Proteinuria first was noted at the age of 2 years. At 13 years, the patient underwent analysis of the CLCN5 gene, which identified missense mutation (I524K) in exon 10. During follow-up, a marked increase in urinary beta2-microglobulin was associated with mild deterioration of renal function. At the age of 15 years, hypocalcemia (7.5 mg/dl) accompanied by an increased plasma concentration of alkaline phosphatase was first detected. At that time, plasma concentration of 25(OH)D3 and 1'alpha25(OH)2D3 were low accompanied by a high plasma parathyroid hormone concentration. A renal biopsy specimen revealed tubulointerstitial alterations including mononuclear cell infiltration, partial fibrosis and focal glomerular sclerosis. Immunofluorescence revealed weak, discontinuous staining of megalin along the brushborder of renal proximal tubules. Western blotting demonstrated decreased urinary excretion of megalin. Thus, clinical manifestations and prognosis may vary in Japanese Dent's disease. Reduced megalin expression may have disturbed calcium homeostasis, leading to osseous disorder in our patient.

Because moderate or severe proteinuria is a representative factor indicative of longterm poor prognosis in IgA nephrology, an anti-proteinuric treatment which can be administered longterm with few side effects is necessary. We report here a comparison of antiproteinuric effects in two patient groups treated with different combination therapies.Group A comprised 12 patients with IgA nephropathy, who had 24-h proteinuria of 0.5 gm(2) or more, moderately severe renal histology, and normal renal function, and were treated with a combination of drugs, i.e., prednisolone, an immunosuppressant (mizoribine), an anti-platelet drug (dipyridamole), and an angiotensin-converting enzyme inhibitor. Group B consisted of 18 patients who had baseline characteristics similar to those of the patients in group A and were treated with our previous protocol (a combination of prednisolone, cyclophosphamide, and dipyridamole). Twenty-four-hour proteinuria and creatinine clearance were measured every 6 months. The primary endpoint was reduction of 24-h proteinuria by less than 25% compared with the baseline value.The proportion of patients that exhibited the primary endpoint, as assessed by the Kaplan-Meier method, was found to be significantly higher in group A than in group B (logrank test; P = 0.024). None of the patients in the two groups experienced serious adverse effects.The results suggested that the use of drugs in combination with cyclophosphamide was beneficial for patients with moderately severe IgA nephropathy. Because moderate or severe proteinuria is a representative factor indicative of longterm poor prognosis in IgA nephropathy, an anti-proteinuric treatment which can be administered longterm with few side effects is necessary. We report here a comparison of antiproteinuric effects in two patient groups treated with different combination therapies.

We describe a patient with IgA nephropathy associated with Crohn disease. IgA nephropathy first appeared at the age of 10 years. Combined therapy with prednisolone, cyclophosphamide, warfarin, and angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year, and remission was maintained. At the age of 13 years, the patient developed Crohn disease and IgA nephropathy recurred. Significant increases in serum IgA were associated with progression of Crohn disease. An elemental diet combined with oral prednisolone resulted in clinical improvement of Crohn disease and in remission of nephropathy and normalization of serum IgA concentration. The clinical course of the two diseases was linked, suggesting a common pathogenetic mechanism involving an IgA immune response to mucosal challenge in the intestine.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor family of growth factors, is synthesized as a membrane-an- chored precursor (proHB-EGF) that is capable of stimulating adjacent cells in a juxtacrine manner. ProHB-EGF is cleaved in a protein kinase C-dependent process, to yield the soluble form. It was observed that HB-EGF acts as a morphogen for the collecting duct system in developing kidneys. HB-EGF protein was expressed in the ureteric bud of embryonic kid- neys. Cultured mouse ureteric bud cells (UBC) produced HB- EGF via protein kinase C activation. After stimulation with phorbol ester (12-O-tetradecanoylphorbol-13-acetate) or re- combinant soluble HB-EGF, UBC cultured in three-dimen- sional collagen gels formed short tubules with varied abundant branches. When proHB-EGF-transfected UBC were stimulated with 12-O-tetradecanoylphorbol-13-acetate and cultured in collagen gels, they exhibited linear growth, forming long tu- bular structures with few branches at the time of appearance of proHB-EGF on the cell surface. The structures exhibited a strong resemblance to the early branching ureteric bud of embryonic kidneys. When UBC were cultured in the presence of transforming growth factor-b and soluble HB-EGF, they formed long tubules and few branches, similar to the structures observed in proHB-EGF-transfected UBC. These cells exhib- ited apical-basolateral polarization and expression of the water channel aquaporin-2. These findings indicate that soluble HB- EGF and proHB-EGF induce branching tubulogenesis in UBC in different ways. Juxtacrine activation by proHB-EGF or the synergic action of soluble HB-EGF with transforming growth factor-b is important for well balanced morphogenesis of the collecting duct system. The initial events in the process of mammalian kidney devel- opment are characterized by proliferation of ureteric bud cells (UBC) and tunneling of these cells into the surrounding undif- ferentiated mesenchyme (1-3). The ureteric bud forms branch- ing tubules, with subsequent differentiation into the collecting ducts. Simultaneously, cells of the metanephric mesenchyme differentiate into epithelial cells that eventually develop into nephrons. These processes can be affected by several locally produced growth factors, including epidermal growth factor (EGF), transforming growth factor-a (TGF-a), hepatocyte growth factor (HGF), glial cell line-derived neutrophic growth

Renal tubular dysgenesis (RTD) is a fatal congenital disease characterized by a defect in the differentiation of the proximal and distal convoluted tubules. This disorder is clinically associated with oligohydramnios, intrauterine growth retardation, and acute renal failure, and the diagnosis is made only at autopsy. We report a very low birth-weight infant with RTD. The infant was delivered at 32 weeks of gestation by cesarian section, because of fetal distress, and weighed 631 g. She had no micturition after birth and developed acute renal failure on day 3 of life. Because ultrasound scan did not show any abnormalities of the kidneys, she was treated aggressively with various blood purification procedures, but she died of sepsis and disseminated intravascular coagulation (DIC) on day 13 after birth. Postmortem examination of the kidneys showed glomerular crowding and undifferentiated tubules. Positive staining of tubular epithelial cells for epithelial membrane antigen supported a diagnosis of RTD. When renal failure occurs in a neonate without any gross morphological abnormalities of the kidneys on ultrasound imaging, RTD should be considered. A review of the literature showed that this is the first case of RTD reported in Japan.

Since isolated C3 mesangial proliferative glomerulonephritis in the absence of systemic disease (i-C3-GN) is an uncommon chronic glomerular disease, long-term prognosis and optimal therapeutic intervention for it are not yet fully defined, especially in children. We report clinical features, outcome, and interventions in 4 patients, ranging from 6 to 18 years old, with i-C3-GN. Microscopic or macroscopic hematuria with or without proteinuria was first noted between 3 and 8 years. When present, proteinuria ranged from 0.2 to 1.0 g/24 h. Persistent hypocomplementemia and circulating immune complexes were found in 1 patient. None of the patients had nephrotic syndrome or hypertension. Percutaneous renal biopsy specimens showed varying degrees of mesangial proliferative glomerulonephritis; 2 patients showed mild mesangial proliferation, while others exhibited moderate histologic severity. In 1 patient with a mild mesangial increase, tubulointerstitial changes were associated. Both patients exhibiting mild mesangial changes followed a benign clinical course with normal renal function over 10 years of follow-up. Patients with moderately severe mesangial alteration manifested slight renal function loss and moderate proteinuria at the time of biopsy, but these largely resolved after a six-month course of prednisolone combined with cyclophosphamide, warfarin, and an angiotensin-converting enzyme inhibitor. Thus, clinical manifestations and the need for aggressive treatment appear to vary among pediatric patients with i-C3-GN. Therapy combining prednisolone with immunosuppression seemed to reduce proteinuria and improve glomerular function in patients with moderately severe mesangial proliferation.

Treatment with hydroxymethylglutaryl coenzyme A reductase inhibitors and thiazolidinedione derivatives may prevent the development of diabetic nephropathy. The precise mechanisms of the beneficial effects of these agents in mesangial cells are uncertain. We cultured mesangial cells from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus. The effects of fluvastatin and/or troglitazone on DNA synthesis were determined. Fluvastatin in combination with troglitazone markedly inhibited DNA synthesis and induced apoptosis in mesangial cells from OLETF rats. Combined therapy with fluvastatin and thiazolidinedione derivatives may be effective for suppression of mesangial cell proliferation in the early phase of diabetes, thereby possibly slowing the evolution of diabetic glomerulopathy.