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)

We examined histopathological changes of the kidney in patients with mixed connective tissue disease (MCTD) including those of glomeruli, arteries and interstitium by morphometric method. All specimens examined were collected from 25 autopsy cases diagnosed as MCTD according to the criteria for this disease proposed by the MCTD committee sponsored by the Japanese government. Clinical evidence of renal dysfunction such as proteinuria was present in 16 out of 25 cases (64%). Histopathologically, membranous type glomerular lesion was found most frequently (40%), followed by membrano-proliferative (6.7%) and mesangioproliferative types (6.7%). Nine cases had no glomerular lesion. Severe arterial lesion such as necrotizing angiitis was not found in our kidney specimens. However, morphometry revealed a high incidence of intimal thickening in the renal arteries of these patients as compared to control cases, showing this to be one of the most common features of MCTD with clinical importance. This type of arterial lesion, also seen in kidneys in other types of collagen diseases, may suggest an etiology common to them. The severity of the renal interstitial lesion in MCTD was intermediate between that of systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS), poly-or dermatomyositis (PM/DM).
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PMID:Morphometric analysis of the kidney lesions in mixed connective tissue disease (MCTD). 790 Jan 53

Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.
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PMID:Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats. 790 49

Passive Heymann nephritis (PHN) is a model of human membranous nephropathy that is characterized by formation of granular subepithelial immune deposits in the glomerular capillary wall which results in complement activation. This is causally related to damage of the filtration barrier and subsequent proteinuria. The local accumulation of injurious reactive oxygen species (ROS) is a major effector mechanism in PHN. ROS may induce tissue damage by initiating lipid peroxidation (LPO). In turn, this leads to adduct formation between breakdown products of LPO with structural proteins, such as formation of malondialdehyde (MDA) or 4-hydroxynonenal-lysine adducts. To examine the role of LPO in the development of proteinuria we have localized MDA and 4-hydroxynonenal-lysine adducts in glomeruli of PHN rats by immunofluorescence microscopy, using specific monoclonal antibodies. By immunogold electron microscopy, MDA adducts were localized to cytoplasmic vesicles and cell membranes of glomerular epithelial cells, to the glomerular basement membrane (GBM), and also to immune deposits. Type IV collagen was specifically identified as being modified by MDA adducts, using a variety of techniques. Collagenase pretreatment of GBM extracts indicated that the NC-1 domain of type IV collagen was a site of adduct formation. When LPO was inhibited by pretreatment of PHN rats with the antioxidant probucol, proteinuria was reduced by approximately 85%, and glomerular immunostaining for dialdehyde adducts was markedly reduced, even though the formation of immune deposits was not affected. By contrast, lowering of the serum cholesterol levels had no influence on the development of proteinuria. These findings are consistent with the premise that ROS-induced glomerular injury in PHN involves LPO and that this results not only in damage of cell membranes but in modification of type IV collagen in the GBM as well. The close temporal correlation of the occurrence of LPO with proteinuria and the ability of probucol to inhibit proteinuria support a causal role for LPO in the the alteration of the glomerular permselectivity which results in proteinuria.
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PMID:Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen. 792 34

Glomerular basement membrane (GBM) damage and proteinuria occurring during the early phase of acute glomerulonephritis are often neutrophil (PMN) dependent. The present study sought to identify the potential roles of PMN derived elastase and reactive oxygen species (ROS) in the pathogenesis of glomerular basement damage in an homologous in vitro model of anti-GBM nephritis using intact PMN. Human PMN (5 x 10(6)), incubated with human GBM (0.5 mg) pretreated with human anti-GBM IgG, degraded 10.3 +/- 1.1% of the GBM type IV collagen in six hours (8 micrograms/hr), and underwent a two-hour respiratory burst. The same number of sonically disrupted PMN solubulized 22.4 +/- 5.1% of GBM under the same incubation conditions. The inclusion of the elastase inhibitors alpha 1 proteinase inhibitor (alpha 1Pi), and a smaller highly-specific synthetic compound (L658,758), reduced degradation by PMN homogenates by 84.8% and 85.7%, respectively, whereas they were only able to inhibit intact PMN mediated degradation by a maximum of 49.2% and 50.9%, respectively. The inclusion of EDTA (10 mM), an inhibitor of metalloproteinases, reduced GBM degradation by APMA activated and disrupted PMN by only 7.5%. Incubation of PMN with diphenylene iodonium (DPI) abolished PMN reactive oxygen species generation by > 95% but preserved elastase release. This compound did not directly affect GBM degradation. It did, however, abolish the inhibitory effect of ROS on alpha 1Pi activity and thus indirectly reduced GBM damage by up to 20%.
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PMID:Relative roles of elastase and reactive oxygen species in the degradation of human glomerular basement membrane by intact human neutrophils. 793 3

An extracellular matrix (collagens I, III, IV) was studied in the glomeruli of patients demonstrating glomerular low density lipoproteins (LDL) and free of them. These two patients' groups were not found significantly different by age, nephropathy duration, blood pressure, serum concentrations of creatinine, triglycerides, HDL cholesterol. The LDL deposit group differed by longer duration of the nephrotic syndrome, higher 24-h proteinuria, lower serum albumin levels, higher total cholesterol in the serum and the proportion VLDL and LDL cholesterol to HDL cholesterol. They had noninflammatory nephropathies more frequently, collagen IV accumulated in the glomerulus more actively, there appeared interstitial collagens I and III. The discussion concerns the role of hypercholesterolemia with the above proportion of cholesterols, its duration, a type of cells dictating mesangial proliferation, in the development of LDL-deposit-induced glomerulosclerosis.
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PMID:[Hyperlipidemia and glomerulosclerosis in nephropathies: clinicomorphological comparisons]. 798 38

The congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria already at birth. The gene locus defective in CNF was searched for using polymorphic markers of candidate genes coding for components of the basement membrane (BM). The linkage analyses in 17 Finnish CNF families demonstrated exclusion of obligatory recombination events between the disease and eight genes coding for BM components. The genes coding for the alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 4(IV) chain of type IV collagen, the B1e, B2e and B2t chains of laminin, as well as the BM heparan sulfate proteoglycan core protein were all excluded in this Finnish family material. Since the defect is not in any of the genes coding for major components of BM, the identification of the gene defect will most probably reveal a new gene important for the development and function of the glomerular basement membrane.
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PMID:Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. 800 2

A 35-year-old male patient clinically characterized by massive proteinuria and hypertension without evidence of systemic diseases is reported. Histological investigation of renal biopsy specimens revealed extensive nodular formations in the mesangial areas in every glomerulus. Light-microscopic examination did not allow discrimination between the glomerular changes found in these specimens and the nodular glomerulosclerosis described in patients with diabetes mellitus. Electron-microscopic examination confirmed the presence of massive, nodular, mesangial expansions consisting of finely fibrillar substances without electron-dense deposits and circumferential mesangial interposition. Immunofluorescent examination showed deposition of IgG, C3, fibrinogen and kappa and lambda light chains in mesangial areas, peripheral capillary loops and a part of the nodules. Furthermore, collagen types IV, V, VI and laminin were detected in the nodules. Amyloid was not observed in these nodules. This diagnosis has not been made, and the mechanism of this nodular glomerulosclerosis remains unknown.
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PMID:Nodular glomerulosclerosis of unknown origin associated with the nephrotic syndrome. 801 53

Molecular organization of extracellular matrix (ECM) in the kidney may change as impairment of renal function progresses. The present immunohistochemical study of the kidney was designed to compare localization of type I, III, IV, V, and VI collagens between "Group A" (13 patients on maintenance hemodialysis due to diabetic nephropathy) and "Group B" (13 patients with diabetic nephropathy and massive proteinuria whose serum creatinine levels were 1.3 +/- 0.5 mg/dl, mean +/- SD). Nodular scleroses that were commonly observed both in Group A (87.8 +/- 10.1%) and B (80.5 +/- 17.0%) were stained in a very similar way with antibodies against collagen types IV, V, and VI. On the contrary, thickened Bowman's capsules that were observed exclusively in Group A (80.7 +/- 10.4% in Group A versus 5.7 +/- 6.2% in Group B) were stained intensely with antibodies against collagen types I and III. Normal and expanded peritubular interstitium from every group was stained with all of the above antibodies in an identical manner. Taken together, these results indicated a close relationship between severe impairment of residual renal function and a high incidence of thickened Bowman's capsule rich in type I and III collagens.
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PMID:Phenotypic expressions of type I, III, IV, V, and VI collagens in patients with diabetic nephropathy: immunohistochemical comparison between HD and non-HD patients. 802 9

A 32-year-old Japanese male presented with abundant proteinuria, and renal biopsy revealed diffuse subendothelial and mesangial deposits in the glomeruli without hypercellularity or mesangial interposition. There was no clinical or laboratory evidence of systemic conditions such as collagen-vascular disease, paraproteinemia, or infection. Treatment with corticosteroid was ineffective and the patient eventually went into end-stage renal failure. To our knowledge, this is the first report of an idiopathic progressive glomerulopathy characterized by diffuse, global subendothelial and mesangial deposits, which suggests to us a novel insight into glomerular subendothelial/mesangial deposition.
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PMID:Idiopathic progressive glomerulopathy with extensive subendothelial and mesangial immune deposit formation. 807 36

In patients with glomerulonephritis widespread crescents are associated with a poor prognosis. Crescent formation appears to depend on the migration of mononuclear cells into Bowman's space, and therefore the interaction between leukocytes and glomerular endothelium may be a critical event in the genesis of crescents. We performed the present study to determine the effects of mouse monoclonal antibodies to the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) in a model of crescentic glomerulonephritis in Wistar-Kyoto rats, induced by immunization with bovine glomerular basement membrane (GBM). By 10-14 d after immunization, the rats had developed circulating anti-GBM antibodies, reactive with the alpha 3 chain of type IV collagen (the Goodpasture antigen), accompanied by proteinuria, accumulation of rat immunoglobulin (Ig)G in the GBM, increased expression of ICAM-1 by glomerular endothelial cells, infiltration of glomerular tufts with LFA-1+ T cells and monocyte/macrophages, and early crescents. At 5 wk all rats had diffuse fibrocellular crescents, glomerular sclerosis, and tubulointerstitial damage. All rats developed severe renal insufficiency and died by 5 or 6 wk. The administration of monoclonal antibodies to rat ICAM-1 and LFA-1 markedly decreased the severity of the renal disease. In a group of rats injected three times a week with the monoclonal antibodies, from 2 d before immunization with GBM to day 14, glomerular abnormalities and proteinuria were virtually absent at day 14; even at 5 wk glomerular disease was quite mild, with only slight crescent formation and with only a mild decrease in renal function. When treatment was continued until 5 wk, the beneficial effects were even more marked, with virtual absence of crescents and with preservation of normal renal function. In a group of rats in which treatment was initiated on day 14, shortly after the appearance of glomerular abnormalities, progression of the disease was appreciably retarded, and the decrease in renal function was inhibited. The kidneys of rats treated from days -2 to 14 with antibodies to ICAM-1 and LFA-1 showed bright linear staining for rat IgG along the GBM, which did not differ in intensity from that seen in untreated rats. Furthermore, the titers of anti-GBM antibodies at 2 wk in treated rats were not lower than that seen in most of the untreated rats. There was, however, moderate reduction of anti-GBM antibodies at 5 wk in the treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis. 809 35


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