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.

Myeloid-related protein (MRP) 8/14 complex is a marker of monocyte and neutrophil activation. We evaluated whether serum MRP8/14 complex is associated with clinical manifestations and pathological findings of Henoch-Schönlein purpura nephritis (HSPN). Patients were divided into two groups based on serum MRP8/14 complex levels at renal biopsy. Group 1 consisted of 18 HSPN patients with less than median (670 ng/ml) MRP8/14 complex levels, and Group 2 of 12 HSPN patients with greater than median levels. Clinical manifestations, laboratory findings and serum E-selectin levels, as a marker of vascular endothelial cell dysfunction, as well as histological and immunohistochemical findings were investigated for both groups. We also measured MRP8/14 complex levels in disease control and healthy control children. Urinary protein excretions, serum MRP8/14 complex levels, and serum E-selectin levels were all higher in Group 2 than in Group 1 patients. Serum MRP8/14 complex levels were higher in HSPN patients than in controls. Serum MRP8/14 complex levels were strongly associated with serum E-selectin levels. Pathological findings revealed that the proportions of patients with ISKDC grades III, IV and V in Group 2 were higher than in Group 1. Our findings suggest that serum MRP8/14 complex levels might be associated with the severity of renal injury and endothelial cell dysfunction in HSPN patients.

RTX-CyAT is effective in FSGS patients with SRNS and may ameliorate the side-effects of PSL and immunosuppressive drugs.

Background. We investigated the efficacy of oral mizoribine pulse therapy (mizoribine-pulse) for cyclosporin (CyA)-dependent, steroid-resistant nephrotic syndrome (SRNS) and frequently relapsing, steroiddependent nephrotic syndrome (FR-SDNS). Methods. One child with CyA-dependent SRNS and eight children with CyA-dependent FR-SDNS were treated with mizoribine-pulse (daily dose: 10 mg/kg; maximum total dose 500 mg). We compared clinical manifestations before and after mizoribine-pulse, and studied the changes in serum mizoribine concentration in each patient on days when mizoribine was administered. Results. Four patients had no subsequent relapses (responders). Two of the four responders discontinued prednisolone and CyA, the other two discontinued CyA. Although each of the five other patients (nonresponders) experienced single subsequent relapses, the dosages of prednisolone and CyA after mizoribinepulse were decreased significantly compared with before mizoribine-pulse. The peak blood concentration of mizoribine in the responders was higher than in the non-responders (3.6±0.9 vs 1.8±0.4 mg/ml). Conclusions. Mizoribine-pulse may be effective for some patients with CyA-dependent SRNS and FR-SDNS.