Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Male ; Renal Insufficiency, Chronic ; metabolism ; pathology

OBJECTIVETo investigate the clinical significance of transforming growth factor-beta 1 (TGF-β1) in children with primary IgA nephropathy (IgAN).

METHODSThirty children who were diagnosed with primary IgAN by renal biopsy between May 2008 and October 2012 were included in the study. Thirty healthy children were used as the control group. Urinary and blood TGF-β1 levels were measured using enzyme-linked immunosorbent assay, and the protein expression of TGF-β1 in the renal tissue was measured by immunohistochemistry. The correlation between TGF-β1 levels in blood, urine, and renal tissue and their relationship with clinical indices were analyzed.

RESULTSChildren with primary IgAN had significantly higher urinary and blood TGF-β1 levels than the control group (P<0.01). Urinary TGF-β1 level was positively correlated with the pathological grade of renal tissue (r=0.557, P=0.001), and a significant positive correlation was also found between the TGF-β1 expression in the renal tissue and the pathological grade of renal tissue (r=0.682, P<0.01). There was no correlation between TGF-β1 levels in blood and renal tissue (r=0.038, P=0.844).

CONCLUSIONSUrinary TGF-β1 level is significantly positively correlated with the pathological severity of disease in children with primary IgAN. Clinical measurement of urinary TGF-β1 may be of great practical value in predicting the progression and prognosis of chronic nephropathy.

Adolescent ; Child ; Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Kidney ; chemistry ; pathology ; Male ; Transforming Growth Factor beta1 ; analysis ; physiology ; urine

China ; Diabetic Nephropathies ; epidemiology ; metabolism ; pathology ; Glomerulonephritis, IGA ; epidemiology ; metabolism ; pathology ; Humans ; Kidney Diseases ; epidemiology ; metabolism ; pathology ; Lupus Nephritis ; epidemiology ; metabolism ; pathology

OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.

METHODSThe renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.

RESULTSThe mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.

CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies

BACKGROUND: Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. RESULTS: The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=0.809, p=0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
Cells, Cultured ; Female ; Glomerular Mesangium/*cytology/metabolism ; Glomerulonephritis, IGA/metabolism/pathology ; Humans ; Immunoglobulin A/*pharmacology ; Male ; Proteins/*metabolism ; RNA, Messenger/*metabolism ; Research Support, Non-U.S. Gov't

OBJECTIVETo examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN).

METHODSRenal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA.

RESULTSThere were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases).

CONCLUSIONSPEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.

Anti-Glomerular Basement Membrane Disease ; metabolism ; pathology ; Antibodies, Antineutrophil Cytoplasmic ; metabolism ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Cell Proliferation ; Epithelial Cells ; metabolism ; pathology ; Glomerulonephritis ; classification ; metabolism ; pathology ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Intermediate Filament Proteins ; metabolism ; Keratins ; metabolism ; Lupus Nephritis ; metabolism ; pathology ; Macrophages ; metabolism ; pathology ; Nerve Tissue Proteins ; metabolism ; Nestin ; Podocytes ; metabolism ; pathology ; Proliferating Cell Nuclear Antigen ; metabolism ; Sialoglycoproteins ; metabolism

Complement C3 ; metabolism ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA ; diagnosis ; metabolism ; Glomerulonephritis, Membranous ; diagnosis ; metabolism ; Humans ; Immunoglobulin G ; metabolism ; Immunohistochemistry ; methods ; Kidney ; chemistry ; pathology ; ultrastructure ; Kidney Diseases ; diagnosis ; metabolism ; Microscopy, Electron ; Nephritis ; diagnosis ; metabolism

CD36 Antigens ; metabolism ; Cell Aggregation ; Cholesterol ; blood ; Foam Cells ; pathology ; Glomerulonephritis, IGA ; blood ; metabolism ; pathology ; Glomerulonephritis, Membranoproliferative ; blood ; metabolism ; pathology ; Glomerulonephritis, Membranous ; blood ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; blood ; metabolism ; pathology ; Humans ; Nephritis ; blood ; metabolism ; pathology ; Nephritis, Hereditary ; blood ; metabolism ; pathology

OBJECTIVETo investigate the effects of astragalus on tubulointerstitial lesions in rats with IgA nephropathy (IgAN) and to explore the possible mechanism.

METHODSTwenty-eight Sprague-Dawley rats were randomly assigned to three groups. The rat model of IgA nephropathy was induced by intragastric administration of bovine serum albumin and injections of LPS and CC14. Six weeks later, the rats with IgAN were randomly treated with oral astragalus (3 g/kg/d, for 6 weeks) or normal saline. Normal control rats which were not subjected to IgAN were treated with normal saline. The number of urinary erythrocytes and urinary protein and B-D-N-Acetyl glucosaminidase (NAG) contents were determined by Pan-automatic biochemistry analyzing meter. Expression of monocyte chemotactic protein-1 (MCP-1) and nuclear factor-kappa B (NF-kappaB) in tubulointerstitial tissues were analyzed by immunohistochemistry. A semiquantitative score was used to evaluate the degree of renal pathologic lesions.

RESULTSThe number of urinary erythrocytes (74.02+/-16.58 / microL vs 383.23+/-4.94 /microL) and urinary protein (13.88+/-4.94 vs 59.82+/-14.73 mg/L) and NAG contents (2.84+/-0.31 vs 5.24+/-0.80 U/L) in the astragalus-treated IgAN rats decreased remarkably compared with those in the IgAN rats without astragalus treatment (P<0.01). Expression of the NF-kappaB and MCP-1 in the renal tissues in the IgAN rats without astragalus treatment was significantly higher than that in the astragalus-treated IgAN rats and normal control rats (P<0.01). There were significant differences in the scores of renal pathologic lesions between the IgAN rats with or without astragalus treatment (6.03+/-0.46 vs 10.57+/-1.23; P<0.01).

CONCLUSIONSAstragalus can decrease the number of urinary erythrocytes and urinary protein and NAG contents, and relieves tubulointerstitial lesions, possibly through the down-regulation of NF-kappaB and MCP-1 expression in rats with IgAN.

Animals ; Astragalus Plant ; Chemokine CCL2 ; analysis ; Glomerulonephritis, IGA ; drug therapy ; metabolism ; pathology ; Immunohistochemistry ; Kidney Tubules ; pathology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; analysis

Mesangial IgA nephropathy was experimentally induced in ddY mice by oral and parenteral administration of the poliomyelitis vaccine (POLIO), and we then tried to investigate if IgA deposition could be prevented by the concurrent use of sodium cromoglycate (SCG), which is known to inhibit the local mucosal immune reaction. Mucosal and systemic immunity could be induced by the administration of POLIO; proteinuria, increased serum IgA levels, mesangial cell proliferation, mesangial matrix widening, mesangial deposits of IgA, and large electron dense deposits in the mesangium were observed. Concurrent administration of SCG and POLIO resulted in a significant decrease in the serum IgA level and mesangial IgA deposits. The later addition or abstinence of SCG after the 70th day did not influence the glomerular mesangial IgA deposition. But the serum IgA level was still decreased by the continuous treatment of SCG even after the 70th day. Thus, mesangial IgA nephropathy simulating IgA nephropathy in humans could be induced in ddY mice using POLIO and its induction could largely be prevented by the concurrent use of SCG. However mesangial IgA deposits already present could not be cleared by the late administration of SCG.
Animal ; Cromolyn Sodium/*pharmacology ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA/*immunology/metabolism/pathology ; Immunoglobulin A/metabolism ; Mice ; Microscopy, Electron ; Poliovirus Vaccine, Inactivated/*immunology