No abstract

These results suggest that EX and ENA have renoprotective effects. The findings also suggest that EXm+ENA provided greater renoprotective effects than those of ENA alone, and that EXm+ENA had some additional peripheral effects without any complications in this rat model.

These results suggest that both exercise and losartan have renoprotective effects, and the combination of exercise and losartan provided greater renoprotective effects than losartan alone, and may affect macrophage infiltration, mesangial activation, and podocyte loss in this model of diabetic nephropathy. It is also suggested that exercise has a specific renoprotective effect that is not related to SBP reduction, and can enhance endurance without renal complications.

Histologic localizations of terminal complement complexes (TCCs) were examined and compared with clinical findings in 154 patients with various renal diseases. Immunohistochemical demonstration of TCCs was carried out on ethanol-fixed paraffin-embedded renal biopsy specimens by indirect immunoperoxidase technique. In glomerular diseases that are thought to be immune-complex glomerulonephritis (IC-GN), such as IgA-nephropathy, membranous nephropathy, and systemic lupus erythematosus (SLE), TCCs were demonstrated in a pattern similar to that of immunoglobulins and C3, indicating that TCCs were induced by immune complexes. The intensity of TCC deposition was correlated with the morphologic destruction of glomeruli or serum creatinine levels in IgA-nephropathy, with urine protein in membranous nephropathy, and with serum C4 in SLE. TCC deposits without IC were also observed in tissue damages without disease specificity such as glomerular or vascular sclerosis and tubulointerstitial lesions. These findings suggested the existence of various roles of TCCs in renal injury, according to IC-mediated or non-IC-mediated mechanism acting in individual diseases.

WT1 and Pax2 are transcription factors involved in kidney development and phenotypic regulation of glomerular epithelial cells. In primary focal segmental glomerulosclerosis (FSGS), the alteration of the podocyte is important for the development of the cellular lesion (CL) and glomerular scar formation. To investigate the contribution of WT1 and Pax2 to the development of the CL in primary FSGS, immunohistological studies were performed using renal biopsy specimens on the expression of WT1, Pax2 and cytokeratin (CK), which is an epithelial marker but never found in normal podocytes. The expression of WT1 was decreased in the CL compared with unaffected podocytes, but Pax2 and CK were expressed significantly in the CL and also in the cells morphologically recognized as podocytes in cases with CL. Our results suggest that re-expression of Pax2 resulting in phenotypic change of podocytes to a different epithelial form is important for the development of the CL in primary FSGS. Normal podocytes resemble mesenchymal cells since they express both vimentin and WT1. In contrast, epithelial cells including parietal epithelial cells of the Bowman's capsule express both Pax2 and CK. Therefore, the mechanism of phenotypic change of podocytes in the CL in primary FSGS might be mesenchymal-epithelial transformation and a developmental paradigm.

No abstract

A retrospective immunocytochemical study was performed on repeated renal biopsy specimens from 47 patients with IgA nephropathy, 23 of whom received steroid therapy after the initial biopsy. Immune cells in renal tissues were detected by the immunoperoxidase method using monoclonal antibodies against common leukocyte antigens, T cells, B cells and monocytes/macrophages.Overall, glomerular infiltration of total leukocytes and monocytes/macrophages was significantly correlated with proteinuria. Interstitial infiltration of total leukocytes, T cells and monocytes/macrophages was significantly correlated with histological injury and renal dysfunction. In the steroid-treated group (group S), urinary protein and glomerular infiltration of total leukocytes and macrophages were significantly reduced at the follow-up biopsy, while these parameters remained unchanged in the nonsteroid-treated group (group N). In group S, interstitial infiltration of almost all of the various cell types, histological renal damage and renal function remained unchanged at the follow-up biopsy, while group N showed a significant increase in the number of interstitial total leukocytes, T cells and macrophages and showed a significant progression of histological renal injury.These findings suggest that glomerular immune cells, especially monocytes/macrophages, are involved in inducing proteinuria and interstitial immune cells are involved in renal deterioration. Furthermore, steroid therapy appears to reduce urinary protein and prevent the progression of tissue injury through suppression of renal infiltration of these inflammatory cells.

We studied infiltrating cells in the glomeruli of eight cases with focal segmental endocapillary proliferation (FSEP) using monoclonal antibodies to leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/M psi). It was demonstrated by sequential biopsies performed in five cases that FSEP preceded focal glomerular sclerosis (FGS). Cell types in FSEP were compared with those in FGS from 17 patients with persistent nephrotic syndrome, ten non-nephrotic patients, and eight patients with nephrotic syndrome which was initially responsive to steroid therapy but relapsed, as well as minimal change specimens from nine nephrotic patients. In the glomeruli, the mean total leukocyte counts increased significantly in the FSEP group (P < 0.01). The serial sections in FSEP revealed that Mo/M psi were the predominant cells and were localized in areas of endocapillary proliferation. T-cell or B-cell infiltration was less marked. The extensive intracapillary distribution of p150,95 antigen belonging to the integrin family and acting as a C3bi receptor suggested that FSEP may be mediated by adhesion molecules expressed on Mo/M psi. These findings indicate that Mo/M psi may play a key role in FGS which shows endocapillary proliferation in the initial stage.