Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brush border of the proximal tubule of human kidney consists of peripheral, integral as well as of transmembranous antigens. Peripheral (surface) antigens are associated with the presence of 5-7 nm globular particles sensitive to limited proteolysis; particles were found to contain a multienzyme complex and exhibited strong affinity towards ConA and WGA. PM-antigens can be solubilized from different portions of PM by differential treatment with proteases and detergents. Labelled antisera against isolated surface glycoproteins reveal a specific reaction with luminal PM of the proximal tubule only, supporting their value for quantitative image analysis (histometry) of kidney tissue sections and for screening of tissue-proteinuria. PM were capable of binding cationic serumproteins (esp. immunoglobulin) and certain O/K-antigens from E.coli, where adhesion was observed on peripheral and intrinsic PM-antigens as well. Major markers of the distal tubule are Tamm-Horsfall protein (cytoplasmic compartment) and a PNA-binding glycoprotein originating from the luminal PM. PM from renal adenocarcinoma exhibit not the globular surface structure found in renal PM, show low immunogenicity, a modulation in the glycosylation pattern of the marker gamma-Glu-transpeptidase and are characterized by a marked depletion of normally differentiated renal antigens. Due to solubilization experiments the presence of cryptic antigens are likely. In addition common determinants between cancer antigens and distinct proteins of the distal tubule and placental trophoblast became apparent.
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PMID:[Characterization of membrane antigens from human kidney and renal adenocarcinoma]. 639 70

The aim of this investigation was to study complement fixation by normal human kidney tissue. C fixation was assessed on acetone-fixed sections of frozen human kidney. In addition, C consumption following incubation of normal fresh human serum with tubular or glomerular fractions of human kidney was measured. The results are consistent with the interpretation that the brush border of proximal tubules of human kidney activates the C system via the alternative pathway. It is suggested that this activation may occur in vivo in patients with a non-selective proteinuria.
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PMID:The brush border of proximal tubules of normal human kidney activates the alternative pathway of the complement system in vitro. 658 97

To evaluate the hypothesis that antibody-mediated damage to proximal tubules (PT) could be a feature of Heymann nephritis (HN), we studied the kidneys of rats in different stages of the disease by light, immunoflourescence (IF), transmission, and scanning electron microscopy. The observations of morphology were correlated with titers of circulating antibodies directed against the brush border (BB) and with proteinuria. Antibody titers reached a maximum 5 to 7 weeks after immunization with Fx1A, coincident with the onset of proteinuria. IgG and C3 were deposited along the BB of PT in all animals within the first week of proteinuria. BB antibodies were present in the urine of those rats. As antibody titers declined, a decrease in the extent of in vivo IgG deposition along the BB was also noted. The results of indirect IF tests, by using BB antibodies on kidneys of rats with HN of 3 to 4 months' duration, suggested extensive loss of the BB antigen(s) from the PT. Numerous granular deposits of IgG were present along the basement membrane of PT at that time. Study of kidney histology revealed that deposition of IgG and C3 along the BB of PT was associated with extensive loss of microvilli, as well as degeneration and proliferation of PT cells. Subepithelial electron-dense deposits were present along the basement membrane of PT. In rats with HN of more than 4 months' duration, with little or no circulating BB antibodies and persistent proteinuria, IgG and C3 were found in minimal amounts along BB. Examination by light and electron microscopy provided evidence of partial recovery of PT lesions in those kidneys. Rats with similar proteinuria resulting from chronic serum sickness did not have similar abnormalities of PT. These observations are consistent with the interpretation that, in rats with HN, BB antibodies induce cytotoxic injury to PT.
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PMID:Antibody-mediated injury to proximal tubules in Heymann nephritis. 700 8

The purpose of this study was to investigate which structures of the nephron, if any, are capable of directly activating the complement (C) system. To this end, two sets of experiments were performed. First, activation of C was assessed on sections of frozen kidney tissue, using the indirect immunofluorescence technique for the demonstration of C fixation. Second, glomerular or tubular fractions of kidney were incubated with normal fresh serum, and subsequent C consumption was measured. The data obtained support the interpretation that the brush border of proximal tubules activates the alternative pathway of the C system. This phenomenon may have pathogenic significance in conditions of aselective proteinuria.
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PMID:In vitro alternative pathway activation of complement by the brush border of proximal tubules of normal rat kidney. 703 53

The sequential changes in renal morphology that occurred for 5 subsequent days after a subcutaneous injection of uranyl nitrate (10 mg. per kg.) were examined in saline- and water-drinking rats using light microscopy, transmission electron microscopy, and scanning electron microscopy. The cortical proximal tubule exhibited diffuse focal brush border loss and increased vacuolization by 1 hour after administration of the nephrotoxin. By 5 days, the P2 and P3 segments were completely necrotic. Cells of P1 segments accumulated large vacuoles throughout their cytoplasm, and distal nephron segments exhibited considerable cellular swelling and vacuolization. Scanning electron microscopy revealed abnormalities in glomerular epithelial cells similar to those seen in humans with chronic renal disease and in experimental animal models characterized by proteinuria. There was essentially no difference in the morphologic response of saline- and water-drinking rats. Although uranyl nitrate administered at this dosage resulted in the relatively slow development of tubular necrosis, changes in renal morphology could be seen within an hour and progressed insidiously throughout the study with little evidence of regeneration.
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PMID:Morphologic changes in uranyl nitrate-induced acute renal failure in saline- and water-drinking rats. 706 22

Autologous immune complex nephritis (Heymann nephritis) is mediated by the autoimmune mechanism and can be induced in certain rat strains by immunization with tubular brush border antigen (Fx1A). The present study was undertaken as a tentative approach to prevent this nephritis, by daily intraperitoneal injections of the solubilized Fx1A for the purpose of removing free antibody from the circulation. Administration of solubilized Fx1A was started a week after the immunization for the induction of Heymann nephritis and continued until the animals were sacrificed at 14 weeks. A control group of immunized animals, also observed for 14 weeks, received saline. The injections of the solubilized FX1A decreased the incidence of proteinuria, the amount of immunoglobulin and complement depositions in the glomeruli, and also the titer of antibody against the brush border. It is concluded that the administration of the solubilized antigen exerts a preventative effect on the course of Heymann nephritis, probably due to removing the antibody from the circulation.
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PMID:Effects of injecting brush border antigen on Heymann nephritis. 711 43

Quantitation of immune deposit formation in glomeruli and correlation with immunohistologic and functional changes has been accomplished only in models of anti-glomerular basement membrane antibody-induced nephritis, or indirectly in immune complex disease by measuring radiolabeled antigen deposition. The kinetics of subepithelial immune deposit formation and the relationship between the quantity of antibody deposited and proteinuria are defined here for the first time in an established model of membranous immune complex nephritis (passive Heymann nephritis) induced by a single intravenous injection of (125)I-labeled sheep immunoglobulin (Ig)G antibody to rat tubular brush border antigen (Fx1A). Measurement of antibody deposition in glomeruli (GAb) isolated from rats injected with 10 mg of anti-Fx1A demonstrated a mean of 12 mug GAb in 4 h, which increased linearly to 48 mug in 5 d. GAb represented only 20 and 44% of total kidney antibody binding at these times. Proteinuria occurred only after 4-5 d of antibody deposition in rats with total kidney antibody binding exceeding approximately 200 mug/2 kidneys. Steroid treatment and vasoactive amine blockade did not significantly alter the quantity or localization of immune deposits. It was also demonstrated that isolated rat glomeruli specifically bound nephritogenic quantities of anti-Fx1A in vitro within hours. Analysis of the quantitative aspects of glomerular antibody deposition in vivo and glomerular antibody binding in vitro provides additional evidence that subepithelial immune deposits in passive Heymann nephritis may form in situ by reaction of free antibody with antigenic constitutents of the normal rat glomerulus. The observed kinetics of deposit formation differ markedly from those in anti-glomerular basement membrane disease and suggest a role for factors in addition to antigen-antibody interaction in determining this unique pattern of glomerular immune deposit formation.
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PMID:Experimental membranous glomerulonephritis in rats. Quantitative studies of glomerular immune deposit formation in isolated glomeruli and whole animals. 740 Mar 10

The only established role for complement in mediating immunologic renal disease involves elaboration of leukochemotactic factors and neutrophil-dependent glomerular injury. In the passive Heymann nephritis (PHN) model of experimental membranous nephropathy, rats injected with sheep antibody to rat proximal tubular brush border antigen (Fx1A) form subepithelial deposits of sheep IgG and rat complement (C3), and develop heavy proteinuria after 5 d without glomerular inflammatory changes. To study the role of complement in mediating proteinuria in PHN, 16 rats were treated daily with cobra venom factor from before antibody injection to maintain C3 levels at < 10% of pretreatment values and compared to 16 untreated controls. Proteinuria at 5 d was abolished in C3-depleted rats (4 +/- 1, controls 70 +/- 15 mg/d, P < 0.001), although renal deposition of 125I-labeled antibody ws the same in both groups (188 +/- 35 vs. 191 +/- 22 microgram IgG/2 kidneys, P > 0.5). Nephritogenic doses of both the noncomplement-fixing F(ab')2 portion and the gamma 2 subclass of anti-Fx1A IgG produced subepithelial deposits of immunoglobulin without C3, but proteinuria did not occur despite glomerular deposition of up to 70 microgram/2 kidneys of gamma 2. However, glomerular deposition of as little as 60 microgram of gamma 1 produced C3 fixation in vivo and heavy proteinuria. No neutrophil exudate could be detected histologically in PHN from the time of antibody injection through development of proteinuria. Proteinuria in five PHN rats depleted of neutrophils to < 200/mm3 with antineutrophil serum was not reduced compared to six controls with normal neutrophil counts (34 +/- 9.6 vs. 25 +/- 10.4 mg/d, P > 0.5). These results demonstrate that proteinuria in the PHN model of membranous nephropathy is complement-dependent and strongly suggest a neutrophil-independent mechanism. Thus a new role for the complement system in mediating immunologic glomerular injury is identified.
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PMID:A new role for complement in experimental membranous nephropathy in rats. 744 Jul 18

Heymann nephritis developed in rats immunized with brush border membrane fractions isolated from rat kidney tubules. Glomerular autoantibodies eluted from cryostat sections of nephritic kidneys reacted in immunoelectron microscopy with the outer surface of isolated brush border membrane vesicles. This indicates that the autoantigens are plasma membrane components. To characterize further the chemical nature of the nephritogenic autoantigens, we treated the brush border membranes with trypsin and sodium deoxycholate, and the solubilized membranes were then fractionated by lectin affinity chromatography. The polypeptide composition of the fractions was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The capacity of the membrane fractions to induce Heymann nephritis was assessed by observing the development of typical renal lesions, antibrush border autoantibodies, and proteinuria in rats immunized with these fractions. The results suggest that the nephritogenic autoantigen is an integral component of the brush border membrane of kidney proximal tubules and has an affinity for Lens culinaris agglutinin. This indicates that it is a glycoprotein and has mannosyl and/or glycosyl groups exposed in its oligosaccharide side chains.
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PMID:Heymann nephritis induced by kidney brush border glycoproteins. 744 31

We investigated the effects of cyclosporin A (CyA) on accelerated passive Heymann nephritis, an experimental model of membranous nephropathy, that is characterized by immune complex deposition on the glomerular basement membrane. The nephritis was induced in rats by injection of antiserum against the antigen located in the renal tubular brush border membrane and sensitization with rabbit gamma-globulin. CyA was administered p.o. at the dose of 2.5, 10 or 20 mg/kg/day for 40 days after the injection of the antiserum. The administration of CyA resulted in marked suppression of proteinuria and hypercholesterolemia in the nephritic rats. In light microscopy, nephritic control rats showed thickening of the glomerular basement membrane and spike formation in the glomeruli. CyA significantly reduced the appearance of the glomerular alteration. The production of antibody was dramatically attenuated by CyA administration. However, CyA did not decrease the number of circulating white blood cells and platelets below the normal level. In conclusion, CyA suppressed the progress of accelerated passive Heymann nephritis in a dose-dependent manner. The effect of CyA is likely attributable to the powerful depression of antibody production.
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PMID:[Effects of cyclosporin A on experimental nephritis in rats (2): Cyclosporin A suppresses the development of accelerated passive Heymann nephritis]. 750 79


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