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

The aim of this study was to determine the relationship of alpha-smooth muscle actin (ASMA) and the proliferation marker Ki-67 of glomerulonephritis (GN). Immunohistochemical stainings with the usual streptavidin-biotin peroxidase method were performed on 86 renal biopsies using monoclonal 1A4 and Ki-67. The results of the quantitative evaluation of ASMA and Ki-67 were analyzed for the correlation between positive value of ASMA and Ki-67 in different GN. ASMA expressions of glomeruli were highest in acute post-infectious GN [APGN; 16.9 Fraction Volume (FV)%], followed by unclassified proliferative GN (UnGN; 12.5 FV%), membranoproliferative GN (MPGN; 8.5 FV%), lupus nephritis (LupusN; 6.3 FV%), IgA nephritis (IgAN; 5.6 FV%), and normal control (0.1 FV%). The Ki-67 staining was considerably elevated in lupusN (4.3 Ki-67 positives/glomerulus), APGN (2.7), MPGN (2.5), UnGN (1.66), IgAN (0.5), compared with that in normal control group (0.1 Ki-67 positives/glomerulus). Ki-67 value in each category of glomerular diseases was significantly different from that in the control biopsies (p<0.004). The relationship between morphometric results of ASMA and Ki-67 was statistically significant regardless of the diagnosis. (rs=0.425, p=0.000, ASMA= 0.1113+0.1665 Ki-67). In conclusion, the immunohistochemical assessment of ASMA and Ki-67 expression in GN might be a reliable indicator for the progression of GN. This study indicates that active cellular proliferation is associated with increased actin deposition in glomeruli.
Actins/*analysis ; Biopsy ; Cell Division ; Glomerulonephritis/*metabolism/pathology ; Human ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Kidney/pathology

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

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

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 morphologic changes of collagen type III glomerulopathy and to investigate the possible cellular origin for collagen III production.

METHODSLight microscopy, immunofluorescent staining, immunohistochemistry (for collagen I, III and IV and alpha-SMA) and electron microscopy studies on 3 renal biopsy cases of collagen type III glomerulopathy were performed.

RESULTSTwo cases presented with nephrotic syndrome, one of which was associated with systemic hypertension. The third case showed renal impairment and renal hypertension. None had any known family history of renal diseases. Light microscopy showed diffuse thickened glomerular basement membrane and expanded mesangium with deposition of weakly PAS-positive homogeneous material not associated with mesangial cell proliferation. Electron microscopy revealed massive collagen fiber deposits in the subendothelial spaces and mesangium. The mesangial cells also contained bundles of microfilaments in the subplasmalemmal regions. Immunohistochemically, the diffuse positivity for type III collagen corresponded to the homogeneous material seen under light microscopy. The staining for type I and IV collagens was negative. Alpha-SMA was expressed in many mesangial cells.

CONCLUSIONSThe diagnosis of collagen type III glomerulopathy can be made on the basis of detailed morphologic examination and ancillary investigations. It is possible that activated mesangial cells may be the cellular origin of collagen III.

Actins ; metabolism ; Adult ; Collagen Type III ; metabolism ; Female ; Glomerular Basement Membrane ; pathology ; ultrastructure ; Glomerulonephritis ; metabolism ; pathology ; Humans ; Male ; Mesangial Cells ; metabolism ; pathology ; Middle Aged

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

OBJECTIVETo study the expression of neonatal Fc receptor in podocytes in human nephritis and immune-induced rat nephritis models: anti-Thy1.1 nephritis and Heymann nephritis.

METHODSThirty-nine cases of renal biopsies were enrolled from September 2009 to February 2010, including 8 cases of minimal change disease, 4 cases of focal segmental glomerulosclerosis, 9 cases of membranous nephropathy, 12 cases of IgA nephropathy and 6 cases of lupus nephritis. Five normal kidney tissue samples adjacent to renal clear-cell carcinoma were served as normal controls. Laser capture microdissection and real-time RT-PCR were used to assess the expression level of FcRn mRNA in glomeruli of various glomerulonephritides, and immunohistochemistry (IHC) of FcRn by SuperVision method was performed. In addition, rat models of mesangial proliferative nephritis (anti-Thy1.1 nephritis) and passive membranous nephropathy (Heymann nephritis) were established and FcRn was examined in renal tissues by IHC.

RESULTSThe FcRn mRNA level in lupus nephritis was statistically higher than that of normal controls (P < 0.05). FcRn protein expression by IHC was seen in lupus nephritis (6/6), membranous nephropathy (6/9) and IgA nephropathy (7/12), significantly higher than that of normal controls (0/5), P < 0.05. Minimal change disease and focal segmental glomerular sclerosis showed minimal or none expression of FcRn (1/8, 0/4 respectively) and not statistically difference from that of normal controls. Furthermore, FcRn expression in podocytes was detected in rat anti-Thy1.1 (3/5) and Heymann nephritis models (2/7) but was not detected in normal controls.

CONCLUSIONSExpression of FcRn in podocytes was up-regulated in immune-induced human nephritis and rat nephritis models of anti-Thy1.1 nephritis and Heymann nephritis. FcRn may play a role in the development of immune-induced glomerulonephritis.

Animals ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Laser Capture Microdissection ; Lupus Nephritis ; metabolism ; pathology ; Male ; Nephritis ; genetics ; immunology ; metabolism ; pathology ; Nephrosis, Lipoid ; metabolism ; pathology ; Podocytes ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Fc ; genetics ; metabolism ; Thy-1 Antigens ; immunology ; metabolism ; Up-Regulation

OBJECTIVETo study the clinicopathologic features of microscopic polyangitis (MPA), and to compare the differences in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive and ANCA-negative patients, as well as in ANCA-positive cases with or without glomerular immunoglobulin deposition.

METHODSThirty-four biopsy-proven cases of MPA were retrieved from the archival files of the Department during the past 7 years. The clinicopathologic characteristics between ANCA-positive and negative patients, as well as between ANCA-positive cases with and without glomerular immunoglobulin deposition, were compared.

RESULTSAmongst the 34 MPA patients studied, about one-fifth to one-half were accompanied by various extrarenal symptoms. Serum ANCA was positive in 26 patients (76.5%). A slight to moderate increase in urinary protein was demonstrated in 31 patients, while 3 patients had nephrotic syndrome. Elevated serum creatinine was detected in 32 cases. Renal biopsy revealed crescentic glomerulonephritis in 24 cases, focal segmental glomerulonephritis in 8 cases, vascular fibrinoid necrosis with inflammation in 7 cases, intimal thickening of arterioles in 24 cases, interstitial inflammatory cells, including neutrophil infiltration (21 cases), in 29 cases. Crescentic formation was more common in the ANCA-positive group than in the ANCA-negative group (P < 0.05). Amongst the 26 ANCA-positive cases, 10 had glomerular immunoglobulin deposits (including 1 case with IgA nephropathy). In general, these cases had a greater degree of proteinuria than those without glomerular immunoglobulin deposits (P < 0.05).

CONCLUSIONSThe diagnosis of MPA relies on histologic examination of renal biopsy and clinicopathologic correlation. Serum ANCA seems important for glomerular crescent formation. Glomerular immunoglobulin deposition may also play a significant role in the exacerbation of proteinuria.

Adult ; Aged ; Antibodies, Antineutrophil Cytoplasmic ; metabolism ; Biomarkers ; Biopsy ; Female ; Glomerulonephritis ; metabolism ; pathology ; Humans ; Immunoglobulin Isotypes ; metabolism ; Kidney ; pathology ; Kidney Diseases ; metabolism ; pathology ; Male ; Middle Aged ; Nephrotic Syndrome ; metabolism ; pathology ; Proteinuria ; pathology ; Retrospective Studies ; Vasculitis ; metabolism ; pathology

Aged ; Diagnosis, Differential ; Fibronectins ; metabolism ; Glomerulonephritis, Membranoproliferative ; pathology ; Humans ; Immunohistochemistry ; Kidney Diseases ; metabolism ; pathology ; Kidney Glomerulus ; metabolism ; pathology ; ultrastructure ; Male ; Microscopy, Electron