Changes in vaccine coverage and incidence of acute gastroenteritis and severe rotavirus gastroenteritis in children <5 years in Shibata City, Niigata Prefecture, Japan.

Rotavirus (RV) vaccines were first introduced in 2011 and adopted for universal vaccination in 2020 in Japan. However, the effectiveness of RV vaccines after being adopted for universal vaccination in 2020 has not been reported. Because of the easy accessibility of clinics in Japan, many children are not usually hospitalized for RV gastroenteritis (RVGE). Therefore, in order to evaluate the impact of the RV vaccine since 2008, we investigated the incidence of hospitalization for RVGE as well as the frequency of children aged < 5 years who received medical treatment for severe RVGE at clinics in Shibata City, Japan. The RV vaccine coverage rate was 94.0% (1,046/1,113) in Shibata City after universal vaccination in 2020; this was a significant increase from previous rates. The incidence per 1000 person - years for RVGE hospitalization and severe RVGE at clinics were significantly higher among children aged < 3 years than in previous time periods. The incidence in children with all acute gastroenteritis (AGE) decreased significantly after universal vaccination during the COVID-19 pandemic. The proportion of severe RVGE among all AGE cases also decreased significantly after universal vaccination among children aged < 3 years (0.0%) and those aged 3-4 years (0.6%). There were significant differences in the distribution of RV genotypes isolated from the feces of children with RVGE between different eras divided by RV vaccination rates, especially G1P[8], which was the major genotype before it recently almost disappeared. Further studies are warranted to assess the impact of the COVID-19 pandemic.

Occurrence of severe rotavirus gastroenteritis in children younger than three years of age before and after the introduction of rotavirus vaccine: a prospective observational study in four pediatric clinics in Shibata City, Niigata Prefecture, Japan.

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 occurrence of severe rotavirus gastroenteritis in children under 3 years of age before and after the introduction of rotavirus vaccine: a prospective observational study in three pediatric clinics in Shibata City, Niigata Prefecture, Japan.

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.

Clinicopathologic features, outcome, and therapeutic interventions in four children with isolated C3 mesangial proliferative glomerulonephritis.

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.

Antiproliferative effect of fluvastatin and thiazolidinedione in mesangial cells of diabetic rats.

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.

Comparison of antiproteinuric effects of two different combination therapies in children with IgA nephropathy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

An adolescent with IgA nephropathy and Crohn disease: pathogenetic implications.

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.

Induction of collecting duct morphogenesis in vitro by heparin-binding epidermal growth factor-like growth factor.

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 kidneys. 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 recombinant soluble HB-EGF, UBC cultured in three-dimensional 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 tubular 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-beta and soluble HB-EGF, they formed long tubules and few branches, similar to the structures observed in proHB-EGF-transfected UBC. These cells exhibited 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-beta is important for well balanced morphogenesis of the collecting duct system.