: Henoch -Schönlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis involving the capillaries and the deposition of IgA immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. Thus, it is important to clarify the onset mechanism as well as the prognostic factors of Henoch -Schönlein purpura nephritis (HSPN) and to identify the most appropriate treatment. We herein review the pathogenesis, the prognostic factors and treatment of HSPN. As to the pathogenesis, several studies suggest that galactose -deficient IgA1 (Gd -IgA1) is recognized by anti -glycan antibodies, leading to the formation of circulating immune complexes and their mesangial deposition, thereby inducing renal injury. With regard to the prognostic factors, a number of factors have been suggested including nephrotic syndrome, decreased factor XIII activity, hypertension, severe renal injury, high renal accumulation of activated macrophage, alpha -smooth muscle actin, and high serum myeloid -related protein levels. For the treatment of severe HSPN, aggressive therapies including multiple drug combination therapy and plasmapheresis have been shown to be effective in ameliorating proteinuria and histological severity. Nevertheless, detailed investigation into the pathogenesis of HSPN and double -blind randomized control studies on children with HSPN are still necessary.

We evaluated the efficacy of tonsillectomy plus pulse prednisolone, warfarin, and dipyridamole including methylprednisolone pulse (tonsillectomy plus pulse therapy), versus prednisolone, warfarin, and dipyridamole including mizoribine (PWDM) for the treatment diffuse IgA nephropathy (IgAN) in children. The patients were randomly assigned to be treated by tonsillectomy plus pulse therapy for 2 years (Group A, n=16) or PWDM for 2 years (Group B, n=16). The clinical features and pathological findings in both groups were analyzed prospectively. The mean urinary protein excretion after 6 months of treatment in both groups had decreased significantly compared with pre-therapy. The activity index (AI) in both groups was lower at the time of the second biopsy than at the time of the first biopsy. The chronicity index (CI) in Groups A and B did not differ between the first and second biopsy. At the latest follow-up examination none (0%) of the patients in either group had renal insufficiency. None of the patients in Group A, but six patients in Group B experienced an acute exacerbation of IgAN as a result of tonsillitis (P<0.05). In conclusion, although there was no untreated control group in this study, the results suggested that tonsillectomy plus pulse therapy is as effective as PWDM in ameliorating proteinuria and histological severity in IgAN patients and in preventing acute exacerbation of IgAN by tonsillitis.

Alpha-smooth muscle actin (alpha-SMA) is the actin isoform that predominates within vascular smooth-muscle cells and plays an important role in fibrogenesis. On the other hand, c-Met is the receptor for hepatocyte growth factor (HGF), which plays a role in protection from injury and has anti-fibrogenetic effects. To clarify whether alpha-SMA and HGF are associated with the progression of renal injury in Henoch-Schönlein purpura nephritis (HSPN), we evaluated the renal expression of alpha-SMA and c-Met in HSPN patients. Patients were divided into three groups. Group 1 consisted of eight patients (male:female 4:4) with stage II or less in the classification of the International Study of Kidney Disease in Children (ISKDC), Group 2 consisted of 20 patients (male:female 11:9) with ISKDC stage III or greater and a good prognosis, and group 3 consisted of seven patients (male:female 3:4) with ISKDC stage III or greater and poor prognosis. Renal biopsy findings, including c-Met and alpha-SMA staining, were investigated for each group. At first biopsy, the mean scores for renal alpha-SMA and glomerular c-Met in groups 2 and 3 were higher than those in group 1, while mean scores for neither renal alpha-SMA nor glomerular c-Met differed between groups 2 and 3. At second biopsy, the mean scores for renal alpha-SMA staining in group 3 were higher than those in group 2, and mean score for glomerular c-Met staining in group 3 was lower than that in group 2. In groups 2 and 3, the mean scores for glomerular and interstitial alpha-SMA staining at first biopsy were correlated with the chronicity index (CI) at second biopsy, but the mean score for glomerular c-Met staining at first biopsy correlated with neither the activity index (AI) nor CI in the first or second biopsies in all groups. Our findings suggest that the expression of renal alpha-SMA may be associated with progression of renal injury in HSPN.

Background : To evaluate the recent frequency of onset and severity of IgA vasculitis with nephri-tis (IgAVN) in Fukushima Prefecture, we examined the epidemiology and clinico-pathological manifestations of IgAVN in our hospital over a 10-year period. Methods : We enrolled 18 patients with IgAVN treated between 2004 and 2013 in the Department of Pediatrics, Fukushima Medical University School of Medicine. These patients were divided into two groups ; Group 1 consisted of 12 patients with IgAVN hospitalized between 2004 and 2008 and Group 2 consisted of 6 patients with IgAVN hospitalized between 2009 and 2013. The epidemiology , clinical features, laboratory data, pathological findings, and outcome were retrospectively compared between the two groups. Results : The numbers of patients with IgAVN per year in Group 2 were lower than that in Group 1. The frequency of patients with higher than grade IIIb disease in Group 2 (50%) was lower than that in Group 1 (94%) ; furthermore, the frequency of patients with higher than grade IV disease in Group 2 (0%) was lower than that in Group 1 (50%). Conclusions : Our findings suggest that the incidence of onset and severity of IgAVN in patients diagnosed between 2009 and 2013 were lower than those in patients diagnosed between 2004 and 2008.

The process of glomerular development consists of four developmental stages: vesicle (V) stage, S-shaped body (S) stage, capillary loop (C) stage and maturation (M) stage. However, the development of glomerular endothelial, mesangial and epithelial cells in fetal and infant kidneys remains unclear. In order to determine the characteristics of human glomerular development, we investigated the process of glomerular development by staining fetal and infant kidneys for CD31, CD34 and FB21, markers for endothelial cells, α -smooth muscle actin (α -SMA), a marker for mesangial cells, and nephrin, a marker for podocytes. These series of studies were carried out on kidneys obtained at autopsy from 27 fetuses and 5 infants. The fetuses were divided into the following 5 groups according to gestational age; 13-19, 20-24, 25-29, 30-34 and 35-39 weeks. In each group, glomerular development was classified according to the developmental stage and the staining patterns for CD31, CD34, FB21, α -SMA and nephrin. The proportion of V-stage development in 100 glomeruli examined was highest at 13-19 weeks. After 20 weeks, the V-stage proportion decreased gradually, and the proportion of S stage became highest at 20-24 weeks. The C-stage proportion was highest at 25-29 weeks, while the M-stage proportion was highest in infants aged 1-6 months. The staining patterns for CD31, CD34 and FB21 were similar in endothelial cells after 25 weeks of gestation. Staining of α -SMA and nephrin was first observed in the S stage. In conclusion, maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage. glomerular development; CD31; CD34; FB21 © 2007 Tohoku University Medical PressThe glomerulus, the most important filtering apparatus in the body, is a unique and highly specialized structure. Three types of cells in the glomerular tufts, the glomerular capillary endothelial cells, mesangial cells and glomerular epithelial cells, can be clearly identified, and their functions

To evaluate whether SP-D concentration is a useful biomarker of the severity of respiratory syncytial virus (RSV) bronchiolitis, we determined SP-D concentrations in patients with RSV bronchiolitis with or without chronic heart disease. We enrolled 52 patients who had been diagnosed with RSV bronchiolitis and required admission to the hospital at the Department of Pediatrics of Fukushima Medical University School of Medicine from 2004 through 2005. These patients were divided into two groups: Group 1 consisted of patients without any underlying disease and Group 2 consisted of patients with chronic heart disease. These patients were assigned to one of three categories. Stage A consisted of patients without oxygen dosage, Stage B of patients who required oxygen dosage, and Stage C of patients required artificial respiration. We evaluated baseline characteristics, clinical features, and serum SP-D concentration in Group 1, Group 2, and a control group (healthy infants without infection). Mean serum SP-D concentrations in patients with RSV bronchiolitis were higher than those in the control group (125.8 ± 49.3 and 44.2 ± 20.1 ng/ml, respectively). Mean serum SP-D concentration was also higher in Group 2 than in Group 1 patients (160.4 ± 56.4 and 112.3 ± 39.4 ng/ml, respectively). Mean serum SP-D concentrations were higher in Stage C than in Stages A or B patients, and mean serum SP-D concentrations were higher in Stage B than in Stage A. These findings suggest that serum SP-D is associated with the severity of RSV bronchiolitis and that it may be a useful biomarker for the severity of RSV bronchiolitis.

We evaluated whether methylprednisolone and urokinase pulse therapy combined with mizoribine (MUPM) was effective in children with severe Henoch-Schoenlein purpura nephritis (HSPN). We studied 12 patients who had been diagnosed with HSPN of at least ISKDC type III. All patients were treated with MUPM. Clinical features, pathological findings, and prognosis were prospectively investigated. Ten patients (responders; nine with ISKDC grade IIIb and one with grade IVb) were treated with MUPM, whereas MUPM was discontinued due to the lack of response in two patients (non-responders; two with grade IVb). Among responders, urinary protein excretion had decreased significantly from 99.7 ± 37.8 to 25.9 ± 33.4 mg/m(2) per hour after 3 months of therapy. The acute index and tubulointerstitial scores decreased significantly from 5.8 ± 1.5 and 3.8 ± 0.6 at the first biopsy to 2.3 ± 1.3 and 1.0 ± 0.8 at the second biopsy, respectively. At the most recent follow-up, eight of the responders had normal urine, and two had minor urinary abnormalities. Non-responders demonstrated continued high levels of urinary protein excretion after 3 months of therapy, and MUPM was discontinued. Our study suggests that MUPM is effective in ameliorating the proteinuria and the histological severity of HSPN in patients with <50% crescents but is not so effective for HSPN in patients with >50% crescents.

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