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)

Human TNF alpha locus locates between HLA-B and DR region on the short arm of chromosome 6. The 5.5 kb and 10.5 kb of TNF alpha restriction fragment length polymorphic (RFLP) bands were identified by Southern hybridization using a restriction enzyme, NcoI. The frequencies of those bands were not different among patients with systemic lupus erythematosus (SLE), those with rheumatoid arthritis and normal controls. In the lupus patients, proteinuria was more frequent in the patients with the 5.5 kb RFLP band (19/39: 48.7%) than those without 5.5 kb band (7/35: 20%) (p less than 0.05). Furthermore, this band was strongly associated with the haplotype HLA B44-DRw13-DQw1. In order to investigate the association between this gene polymorphism and the production of TNF alpha, peripheral blood mononuclear cells from patients with SLE and normal controls were cultured for 24 hours with lipopolysaccharide and concanavalin A and the amount of TNF alpha in the supernatant was measured by enzyme linked immunosorbent assay. The TNF alpha production of lupus patients was not statistically different from that of normal controls. The production of TNF alpha was not related to 5.5 kb RFLP band, but in the patients with SLE, the mean value of TNF alpha in patients with the 5.5 kb RFLP band tended to be higher than those without the band. Lupus patients were divided into two groups by the production of TNF alpha i.e. low TNF alpha inducibility group and high TNF alpha inducibility group. Patients with proteinuria were more frequent in patients of the high TNF alpha inducibility group than those of low TNF alpha inducibility group (p less than 0.05). There were four patients with HLA B44-DRw13-DQw1 who had the 5.5 kb RFLP band and three of them belonged to the high TNF alpha inducibility group with nephrosis. These data suggest that TNF alpha and HLA are possibly associated with the severity of lupus nephritis.
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PMID:[Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by restriction fragment length polymorphism and production by peripheral blood mononuclear cells]. 135 65

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
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PMID:Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. 767 12

The pathogenesis of idiopathic nephrotic syndrome (minimal change nephropathy and its variants) is not completely understood. In recent years it has been speculated that a cytokine released by circulating blood mononuclear cells could alter the permeability of the glomerular capillary wall. In this study we have explored the potential participation of tumour necrosis factor alpha (TNF alpha), a cytokine mainly produced by monocytes, in 25 children with idiopathic nephrotic syndrome. TNF alpha was determined by cytotoxicity bioassay in the L-929 cell line and by double antibody/RIA. Patients in activity had higher serum TNF alpha levels and TNF alpha production by monocytes than patients in remission and controls. TNF alpha mRNA expression in blood mononuclear cells was analysed by Northern blot. The TNF alpha mRNA levels in patients in activity were increased compared to controls and to patients in remission. No significant differences in IL-1 beta and IL-6 synthesis were found between patients and controls. Our results suggest that TNF alpha, but not other cytokines such as IL-1 beta and IL-6, could play a role in the pathogenesis of the proteinuria in idiopathic nephrotic syndrome.
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PMID:Increase of tumour necrosis factor alpha synthesis and gene expression in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome. 770 73

The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in the therapeutic intervention of anti-GBM Ab GN.
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PMID:Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis. 790 69

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that developing in non-treated rats at 24 weeks. Activation of graft endothelium and/or host leucocytes increased the pace of graft infiltration and the expression of cytokines and other molecules. These events accelerate the process of chronic rejection.
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PMID:Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts. 883 48

Complete examination of 21 patients with IgA nephropathy included determination urine and serum IL-6, TNF alpha and INF gamma levels by ELISA (Luzernachen, Luzern Switzerland). Control group included 15 healthy volunteers. Urine IL-6 levels ranging 37-274.1 pg/ml were detected in 15 (71.2%) patients with IgA nephropathy. IL-6 serum levels were undetectable. In the control group serum and urine levels were also undetectable. Correlation between the IL-6 level and proteinuria degree and endogenous creatinine clearance rate has not revealed statistically significant relationship. In relation to histologic groups (minimal changes, focal glomerulonephritis, mesangial proliferative, diffuse sclerosing) patients with minimal changes had (statistically) significantly higher IL-6 urine levels than the third and fourth group. Average the urine levels were 145.8 +/- 166.6 pg/ml and the serum ones were 148 +/- 101 pg/ml. In relation to the control group (statistically) significant difference was not found. Correlation between TNF alpha level and proteinuria degree and creatinine clearance rate has revealed (statistically) significant relationship (p < 0.05). Average interferon gamma serum levels in lgA nephropathy patients were 312.0 +/- 111.8 and in comparison with the control group (statistically) significant difference was found (p < 0.01). The obtained results suggest the important role of cytokine production disregulation associated with the pathogenesis of IgA nephropathy.
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PMID:[Correlation of inflammatory cytokines in the urine and serum with clinico-laboratory and pathohistologic features in patients with IgA nephropathy]. 910 24

A case in which the enterotoxins of Staphylococcus aureus may have served as bacterial superantigens is presented. This 71-year-old man developed proteinuria and renal dysfunction after contacting pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), coagulase type II. The infection occurred after surgery for recurrent lung cancer. Staphylococcus enterotoxins B, C, and TSST-1 were detected from the bacillus. Ten days after the onset of pneumonia, proteinuria was noted; urinary protein was as high as 1.8 g/day. The serum creatinine was elevated from 1.0 mg/dl to 3.7 mg/dl. Several immunological reactions were detected; the serum levels of IgG and IgA were increased, and the selective usage of T-cell receptor V beta (TCRV beta) was observed. Serum levels of IL-1 beta, IL-2, IL-6, IL-8, IL-12, and tumor necrosis factor alpha (TNF alpha) were also elevated. Examination of the renal biopsy specimen by light microscopy showed minor to mild mesangial proliferative glomerulonephritis. Immunofluorescence microscopy demonstrated the deposition of IgG, IgA, and C3, mainly along the capillary walls. Electron microscopy revealed electron dense deposits, mainly in the subepithelial areas, and injury to the glomerular basement membrane. When the pneumonia improved following antibiotic therapy, the renal function also improved, and proteinuria decreased. The levels of immunoglobulins and the usage of TCRV beta also decreased. Because staphylococcus enterotoxins act as superantigens, we believe this to be a typical case of superantigen-related glomerulonephritis.
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PMID:A case of superantigen-related glomerulonephritis after methicillin-resistant Staphylococcus aureus (MRSA) infection. 940 16

To determine the clinical significance of anti-endothelial cell antibodies in mixed connective tissue disease (MCTD), we measured the titers of antibodies to both untreated and cytokine-treated endothelial cells (EC) in the sera of the MCTD patients by means of an enzyme linked immunosorbent assay. The mean titer of antibodies to untreated EC (aEC) in the sera of the MCTD patients was significantly higher than that for the healthy subjects. The mean titer of antibody to EC treated with IFN gamma, IL1 (aIL1-EC) or TNF alpha (aTNF-EC) was significantly higher than that of aEC in the sera of the MCTD patients with proteinuria, and the mean titer of aTNF-EC was significantly higher than that of aEC in the sea of the MCTD patients with pulmonary fibrosis. Furthermore, the mean titers of aIL1-EC and aTNF-EC in the sera of the MCTD patients with pulmonary fibrosis were significantly higher than those of aIL1-EC and aTNF-EC in the sera of the MCTD patients without pulmonary fibrosis. These results suggest that antibodies to cytokine-treated EC may play a more important role in the manifestation of renal or pulmonary lesions in MCTD patients than aEC.
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PMID:Anti-endothelial cell antibodies in the sera of patients with mixed connective tissue disease--the clinical significance. 943 81

Prospective study was performed on the concentrations of inflammatory cytokines IL-1, TNF and IL-6 in serum and urine (ELISA tests) were determined in the scope of total clinical-laboratory and histologic treatment in 59 patients with primary IgA nephropathy. Control group consisted of 20 healthy subjects. IL-6 was not detected either in serum of patients with IgAN, or in control examinees. TNF alpha and IL-1 beta were detected in control patients' sera and in patients with IgAN, but detected concentrations were not significantly different. IL-1 beta in urine was detected in 82.8%, TNF alpha in 90.0%, and IL-6 in 40% of our patients with IgAN. The concentrations of IL-1 beta were significantly higher compared to IL-1 beta concentrations in urine of healthy subjects and significantly correlated with the severity of glomerular and tubulointerstitial changes, as well as with the degree of proteinuria. Direct and indirect toxicity of TNF alpha on renal structures was confirmed in significantly higher concentrations of that cytokine in urine of patients with mesangial sclerosis of different percentage compared to the patients with isolated mesangial hypercellularity. Also in the patients with index of chronic lesion over 7 significantly higher TNF alpha concentrations in urine were found compared to the patients with lesion index 0-3 and 4-7. Creatinine clearance was in negative correlation with TNF alpha concentrations in urine of our patients with IgAN. Concentrations of IL-6 in urine were in correlation neither with laboratory parameters of renal function, nor with the degree of histologic changes.
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PMID:[Significance of inflammatory cytokines in the pathogenesis of IgA nephropathy]. 962 40

TNF is a key proinflammatory cytokine playing a central role in the expression of endothelial adhesion molecules required for the recruitment of inflammatory cells. Proliferative glomerulonephritis induced by anti-GBM antibody is characterized by the recruitment of inflammatory cells into the glomerulus and capillary damage followed by regeneration with crescent formation. The glomerular pathology may be due to TNF induction and we therefore tested this hypothesis in TNF alpha/beta deficient mice. Anti-GBM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonuclear leucocytes. Distinct proteinuria precedes proliferative glomerulonephritis with glomerular crescent formation, which is fully developed at 10 days. By contrast, no glomerulonephritis developed in TNF alpha/beta deficient mice. Comparable antibody complex deposits are found, but the upregulation of ICAM-1 and VCAM-1, the influx of inflammatory cells and the subsequent tissue damage is absent in TNF alpha/beta deficient mice. Therefore, we conclude that TNF plays a key role for the recruitment of inflammatory cells by preventing the upregulation of endothelial adhesion molecule and the subsequent development of proliferative glomerulonephritis.
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PMID:Failure to induce anti-glomerular basement membrane glomerulonephritis in TNF alpha/beta deficient mice. 1031 26


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