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)

Congenital nephrosis of the Finnish type (CNF) is a hereditary renal disease of unknown aetiology manifested by massive proteinuria of the newborn and unresponsive to any treatment. In this study kidney samples and cultured glomerular mesangial cells from five patients with CNF were studied by indirect immunofluorescence microscopy for the presence and location of major basement membrane matrix (GBM) components. Histological changes of glomeruli ranging from mild thickening of basement membranes to total obliteration and sclerosis were seen. Notably, thickening of the subepithelial layer of Bowman's capsules was regularly seen along with hypercellularity at the juxtaglomerular areas. The matrix components studied (laminin, plasma- and cellular fibronectin, type IV collagen, including the NC-1, alpha-1 and alpha-3 chains, heparan sulphate proteoglycan (HSPG) core protein, thrombospondin) were characteristically seen within the glomeruli. Local thickenings alternating with total loss of epitopes along the GBM were seen, especially with anti-type IV collagen and anti-HSPG antibodies. Sera from CNF patients after transplantation failed to show antibodies against GBM structures in immunofluorescence microscopy, suggesting that no missing epitopes of GBM are introduced with the transplant kidney. Cultured mesangial cells of CNF glomeruli also showed continued in vitro production of the matrix components and their incorporation into the matrix underneath the cell layer.
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PMID:Congenital nephrosis of the Finnish type (CNF): matrix components of the glomerular basement membranes and of cultured mesangial cells. 769 21

The role of the beta 2 integrin cell adhesion molecules (CAM) in directing neutrophil accumulation and injury in acute anti-glomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) was assessed in rabbits by in vivo inhibition of CD18 dependent neutrophil/endothelial cell interactions using a monoclonal anti-CD18 antibody. Rabbits given horse anti-rabbit GBM antibody developed significant glomerular neutrophil influx (2.9 +/- 0.1 neutrophils per glomerular cross-section [c/gcs], normal 0.1 +/- 0.1 c/gcs, P = 0.002) and proteinuria (1389 +/- 257 mg/16 h, normal 15 +/- 4 mg/16 h, P = 0.0015) after 16 h. Rabbits rendered neutropenic (< 500 neutrophils/microL) by mustine hydrochloride, or complement depleted by cobra venom factor, did not develop glomerular neutrophil accumulation and had markedly reduced proteinuria after anti-GBM antibody, demonstrating complement-induced neutrophil recruitment is a major mechanism of glomerular injury in this model. Anti-CD18 antibody treatment of rabbits developing anti-GBM GN abrogated dermal neutrophil influx in response to intradermal injection of fMLP and zymosan activated serum. Treated rabbits achieved levels of anti-CD18 antibody in their serum which saturated the binding sites on rabbit neutrophils in vitro, and their circulating neutrophils had saturated anti-CD18 antibody binding in vivo. However, glomerular neutrophil influx (3.5 +/- 0.4 c/gcs) and proteinuria (1210 +/- 428 mg/16 h) were both unaffected. Thus, in this model of antibody-initiated complement and neutrophil-dependent glomerular injury, in which neutrophil transmigration across the endothelium is not required, effective functional inhibition of beta 2 integrin CAM in vivo did not reduce glomerular injury or glomerular neutrophil influx. These studies demonstrate that beta 2 integrin CAM are not a requirement for neutrophil accumulation and glomerular injury in anti-GBM GN in rabbits.
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PMID:Beta 2 integrin independent neutrophil recruitment and injury in anti-GBM glomerulonephritis in rabbits. 769 18

To clarify the clinical and pathological significance of thin glomerular basement membranes (Thin-GBM) appearing in evident diabetics, we examined the renal biopsies from 179 diabetes mellitus (DM) patients with urinary abnormalities in which the number of non insulin dependent diabetes mellitus cases was 140 cases while the remaining 39 cases had insulin dependent diabetes mellitus. In addition, 17 of these cases were found to have either segmental or diffuse Thin-GBM by electron microscopy. The clinical and morphological parameters between the diabetics with Thin-GBM (DM-Thin-GBM) and the diabetics without Thin-GBM (the controls) were significantly different regarding DM duration (DM-Thin-GBM vs control: 5.3 +/- 5.5 vs 9.8 +/- 6.5 years, p < 0.01), Ccr (67.0 +/- 25.5 ml/min vs 45.6 +/- 24.4 ml/min, p < 0.01), the incidence of hematuria (52.9% vs 24.5%, p < 0.05) and hypertension (13.3% vs 51.3%, p < 0.05). The severity of glomerular damage was mild in the DM-Thin-GBM group as compared to the control. The renal survival rate from the onset of urinary abnormalities was higher in the DM-Thin-GBM group than in the control (p < 0.01). In the case of DM-Thin-GBM, the grade of proteinuria correlated with the mean width of the thickened GBM (p < 0.01) and the spread of the thickened GBM which was more than 500 nm in width (p < 0.001). The severity of microscopic hematuria correlated with the spread of the Thin-GBM (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thin glomerular basement membrane in diabetic patients with urinary abnormalities. 852 10

The involvement of adhesion molecules in the accumulation of inflammatory cells in the glomeruli and subsequent glomerular injury was examined in accelerated-type anti-GBM nephritis in rats. This animal model is known to be manifested by progressive and irreversible glomerular damage with rapid influx of monocytes/macrophages into the glomeruli. Up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in this model. Therefore we examined the effect of ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) in the pathogenesis of this nephritis. Four groups of rats with accelerated-type anti-GBM nephritis were investigated. The first group was the control group injected with normal mouse IgG 2mg/Kg. The second group was administered mouse anti-rat ICAM-1 monoclonal antibody (1A-29) 2 mg/Kg. The third group was administered mouse anti-rat LFA-1 beta monoclonal antibody (WT-3) 2mg/Kg. The fourth group received both 1A-29 1mg and WT-3 1mg/Kg. Proteinuria and the influx of monocytes/macrophage in this model were decreased after the administration of 1A-29 or WT-3. Simultaneous administration of both antibodies showed intense suppression of the proteinuria and marked reduction of the infiltrating cells. These results suggested that the ICAM-1/LFA-1 pathway is critically involved in the pathogenesis of accelerated-type anti-GBM nephritis in rats.
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PMID:[Antinephritis effect of anti-ICAM-1 monoclonal antibody and anti-LFA-1 monoclonal antibody on accelerated-type anti-GBM nephritis in rats]. 790 66

The change of anionic sites on GMB was studied in both adriamycin induced nephrosis and nephrotoxic serum nephritis in rats by means of calculating the PEI stained particles under electron microscope. The results showed that the number of anionic sites within lamina rara externa of GMB was reduced significantly in both kinds of proteinuria rats and the size of anionic sites was also changed, especially in the segments of GBM with fused foot processes. The results demonstrate that the loss of anionic sites on GBM and the functional damage to the charge selective barrier of glomeruli may play an important role in proteinuria of these animal models.
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PMID:[Anionic site changes on glomerular basement membrane (GBM) in proteinuria rats]. 803 79

HgCl2 induces the synthesis of anti-GBM Abs with the development of glomerular and interstitial nephritis, as well as proteinuria, in the Brown Norway rat. The development of this autoimmune disease is a consequence of the appearance of an autoreactive T cell subset-inducing activation of B cells. The administration to mercury-treated rats of the mouse anti-human VLA alpha 4 HP2/1 mAb, which cross-reacts with the rat homologue integrin, completely abrogated the interstitial cell infiltrates. As demonstrated by peripheral blood analysis, this effect is not a result of the depletion of circulating leukocytes or leukocyte subsets. Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria. Our results confirm that in vivo alpha 4 functions in adhesive interaction of circulating leukocytes and vascular endothelium, and is centrally important in the extravasation and migration of T lymphocytes to sites of tissue injury. We also found a complete absence of interstitial cell infiltrates, together with a positive glomerular IgG lineal deposition pattern, when anti-GBM Abs were passively transferred to rats pretreated with anti-alpha 4 mAb, thus indicating an independent role of alpha 4 integrin in both extravasation of immune cells and production of autoantibodies. Furthermore, these in vivo findings provide preliminary evidence for the participation of the VLA-4 integrin in mediating the intercellular interaction of leukocytes regulating the production of Abs, most likely through the existence of additional yet unknown ligand(s).
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PMID:Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin. 805 27

The involvement of adhesion molecules in the glomerular accumulation of inflammatory cells and subsequent glomerular injury was examined in WKY rats with nephrotoxic serum nephritis. This model is characterized by early infiltration of CD8-positive NK cells, followed by influx of monocytes/macrophages into the glomeruli. At day 1 and later, up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in association with the influx of CD8-positive cells and monocytes/macrophages. These cells expressed lymphocyte function-associated Ag-1 (LFA-1). Repeated injection of mAb against rat ICAM-1 or alpha-subunit of LFA-1 (LFA-1 alpha) dose dependently prevented the development of proteinuria, the influx of these cells, and subsequent crescent formation in this nephrotoxic serum nephritis model. Furthermore, simultaneous administration of anti-ICAM-1 mAb and anti-LFA-1 alpha mAb exerted additive protective effects against urinary protein excretion and crescentic glomerulonephritis. Binding of anti-GBM antibody to the glomeruli and production of circulating anti-rabbit IgG antibody were unaffected by injection of these mAb. These results indicate that adhesion of CD8-positive cells and monocytes to glomerular endothelial cells through the LFA-1/ICAM-1 pathway is crucial for the initiation and subsequent progression of nephrotoxic serum nephritis in WKY rats.
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PMID:Antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis. 809 6

Despite the availability of different classifications for rapidly progressive glomerulonephritis (RPGN), patients with "idiopathic crescentic GN" have not been yet inserted as a precisely defined subgroup, pointing to their probable heterogenicity. Trying to better define their characteristic, we retrospectively analyzed the clinical, histological and immunopathological features of 41 patients diagnostically labelled "idiopathic RPGN" because they had no evidence of systemic disease (including systemic vasculitis), no anti-GBM mediated glomerulonephritis and no clearly defined primary glomerulopathy. Starting by a thorough morphological review, 2 subgroups were defined: group I (25 patients) with variable degrees of intraglomerular necrosis, and group II (16 patients) with no intracapillary necrotizing lesions. Group I showed no or minimal endocapillary proliferation, intense interstitial infiltrates with periglomerular localization, frequent ruptures of Bowman's capsule and mild degree of glomerular and/or interstitial sclerosis. 16 patients in this group (64%) had irregular deposits of complement C3 at immunofluorescence while the remaining 9 (36%) had no immune deposits. Clinically they had no previous history of preceding urinary abnormalities, had a mean of 1.8 g/day proteinuria and a positivity for ANCA in 92% (12/13). In group II there was frequently marked mesangial proliferation, scarce interstitial infiltrates, no ruptures of Bowman's capsule and marked degrees of glomerulosclerosis and interstitial fibrosis. All patients in this group had clearly defined immune deposits of C3 and/or IgG. Clinically 50% of these patients had a history of recurrent microhematuria and/or proteinuria, a mean of 4.5 g/day proteinuria and negativity for ANCA in all 8 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Critical re-evaluation of 41 cases of "idiopathic" crescentic glomerulonephritis. 813 64

Antiglomerular basement membrane (anti-GBM) antibody-mediated disease is usually characterized by a rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. We report a case of anti-GBM-mediated nephritis that presented with hematuria and proteinuria. There was no evidence of renal insufficiency or pulmonary hemorrhage. Clinicians should be aware of this rare presentation of anti-GBM-mediated nephritis.
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PMID:Antiglomerular basement membrane antibody-mediated nephritis with normal pulmonary and renal function. A case report and review of the literature. 814 Nov 87

Integrins play a major role in cell-matrix interactions. They alter cellular functions upon binding to matrix proteins or following cross linking and can in turn be regulated by other stimuli acting on the cell. In the kidney integrins may help regulate cellular proliferation and matrix turnover during renal injury, effects which could play an important role in the pathogenesis of glomerulosclerosis and the resultant loss of renal function. Alterations in cell adhesiveness may contribute to tubular epithelial cell sloughing and tubular obstruction in acute renal failure and may play a role in alterations of glomerular capillary wall permeability, leading to proteinuria. Adhesion molecules on GEC may be important targets of antibodies in several models of proteinuric renal disease and areas of GEC detachment from the GBM may be involved in the development of glomerulosclerosis. Since integrins are major links between the ECM and cells, better understanding of their function in the normal kidney and during injury is of importance to a better understanding of the pathogenesis of renal disease.
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PMID:Integrin matrix receptors in renal injury. 815 6


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