Biopsy ; Female ; Glomerular Basement Membrane ; metabolism ; Hashimoto Disease ; metabolism ; pathology ; Humans ; Kidney Diseases ; metabolism ; pathology ; Middle Aged ; Proteinuria ; metabolism ; pathology ; Sjogren's Syndrome ; 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

Wilson's disease is an autosomal recessive disorder of copper metabolism in individuals with mutant ATP7B genes. Impairment of normal excretion of hepatic copper results in toxic accumulation of the metal in liver, brain and other organs. Clinical manifestations include hepatic, neurologic or psychiatric disturbances. Penicillamine, as a chelator of copper, is the drug of choice in the treatment of Wilson's disease but after treatment of penicillamine, granulocytopenia, thrombocytopenia, the nephrotic syndrome, Goodpasture's syndrome, pemphigus vulgaris or pleural effusion may supervene. We report a case of macromastia with multiple fibroadenomas in a patient who was treated with penicillamine for Wilson's disease.
Agranulocytosis ; Anti-Glomerular Basement Membrane Disease ; Brain ; Copper ; Fibroadenoma* ; Hepatolenticular Degeneration* ; Humans ; Liver ; Metabolism ; Nephrotic Syndrome ; Pemphigus ; Penicillamine ; Pleural Effusion ; Thrombocytopenia

It is well known that the glomerular basement membrane heparan sulfate proteoglycan(GBM HSPG) synthesized by glomerular epithelial cell(GEC) has an important role in the permeability of glomerular basement membrane and cyclic AMP(cAMP) is involved in regulation of a wide variety of genes maybe including GBM HSPG gene. The direct effect of cAMP on GBM HSPG gene expression and metabolism was not evaluated as yet. Proteinuria represents an impairment of permselectivity function of glomerular basement membrane regulated by GBM HSPG and could be associated with increased glomerular level of cAMP in nephrotic syndrome of diverse causes. RPD-I(rat GBM HSPG core protein domain-I) detected a >9.5kb transcript of GBM HSPG in RNA of rat GEC. Emp1oying a riboprobe synthesized from RPD-I in RNase protection assay, we examined whether cAMP regulated perlecan expression in the GEC. At l, 6, 24 and 48 hrs of incubation, l mM cAMP caused 43%, 32%, 47% and 40% reduction in mRNA expression of perlecan, respectively. Immunoprecipitation showed a corresponding reduction of 51%, 70% and 68% in the synthesis of 35SO4 labeled GBM HSPG by the GEC fol1owing l2, 24 and 48 hrs of incubation with cAMP. Our results show that decrease in GBM HSPG gene expression and synthesis by cAMP may be of relevance to proteinuric states characterized by activation of these mediators.
Animals ; Cyclic AMP* ; Epithelial Cells* ; Gene Expression ; Glomerular Basement Membrane* ; Heparan Sulfate Proteoglycans* ; Heparitin Sulfate* ; Immunoprecipitation ; Metabolism ; Nephrotic Syndrome ; Permeability ; Proteinuria ; Rats* ; Ribonucleases ; RNA ; RNA, Messenger

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

An early feature of diabetic nephropathy is the alteration of the glomerular basement membrane (GBM), which may result in microalbuminuria, subsequent macroproteinuria, and eventual chronic renal failure. Although type IV collagen is the main component of thickened GBM in diabetic nephropathy, cellular metabolism of each alpha chains of type IV collagen has not been well studied. To investigate the regulation of alpha(IV) chains in diabetic conditions, we examined whether glucose and advanced glycosylation endproduct (AGE) regulate the metabolism of each alpha(IV) chains in the diabetic tissue and glomerular epithelial cells (GEpC). Glomerular collagen alpha3(IV) and alpha5(IV) chains protein were higher and more intense in immunofluorescence staining according to diabetic durations compared to controls. In vitro, mainly high glucose and partly AGE usually increased total collagen protein of GEpC by [3H]-proline incorporation assay and each alpha(IV) chain proteins including alpha1(IV), alpha3(IV), and alpha5(IV) in time-dependent and subchain-specific manners. However, the changes of each alpha(IV) chains mRNA expression was not well correlated to the those of each chain proteins. The present findings suggest that the metabolism of individual alpha(IV) chains of GBM is differentially regulated in diabetic conditions and those changes might be induced not only by transcriptional level but also by post-translational modifications.
Animals ; Cells, Cultured ; Collagen Type IV/genetics/*metabolism/physiology ; Diabetic Nephropathies/*metabolism ; Epithelial Cells/*metabolism ; Glomerular Basement Membrane/metabolism ; Glucose/metabolism ; Glycosylation End Products, Advanced/metabolism ; Male ; Podocytes/*metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis.

METHODSFive cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy.

RESULTSThe glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage.

CONCLUSIONSCollagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.

Basement Membrane ; metabolism ; Biopsy ; Collagen Type III ; genetics ; metabolism ; Female ; Fluorescent Antibody Technique ; Glomerular Mesangium ; metabolism ; Humans ; Immunohistochemistry ; Kidney Diseases ; etiology ; pathology ; Kidney Glomerulus ; pathology ; Microscopy, Electron ; Prognosis ; Proteinuria ; diagnosis

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