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)

Acute glomerular injury in the rat has been induced by the intrarenal, intraarterial infusion of sheep antibody to glomerular basement membrane (antiglomerular basement membrane). The antiglomerular basement membrane antibody has been verified to be of the variety that is complement and neutrophil dependent for the induction of acute proteinuria, which peaks during the first 24 hours. Following injection of the antibody, acute, intense, glomerular injury resulted, with the denuding of glomerular vascular basement membrane associated with extensive damage or destruction of glomerular endothelial cells and fusion of epithelial cell foot processes. Treatment of animals with catalase produced, in a dose-dependent manner, as much as 75% protection against glomerular injury, as assessed by reduction in the proteinuria. Treatment of animals with superoxide dismutase caused a small reduction in the degree of glomerular injury, again assessed by a reduction in proteinuria. However, this protective effect of superoxide dismutase was not found to be statistically significant. The hydroxyl radical scavenger, dimethyl sulfoxide, which has been shown to protect against endothelial cell injury following systemic activation of complement, was not protective in the anti-GBM model. Morphologically, glomeruli from catalase-protected rats showed numerous neutrophils but little or no evidence of injury of either glomerular endothelial or epithelial cells. These data suggest that acute glomerular injury produced by antiglomerular basement membrane is related to H2O2 production from activated neutrophils.
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PMID:Evidence for the role of oxygen radicals in acute nephrotoxic nephritis. 609 Aug 9

It has been shown that Brown-Norway rats develop an immune-type glomerulonephritis after treatment with various mercury-containing drugs. Anti-GBM antibodies were involved, at least in some animals. This glomerulonephritis induced a proteinuria. Strong evidence is given, suggesting that most mercury compounds, some of which, such as mercurial antiseptics, are widely used, could induce an immune-type glomerulonephritis. The question therefore arises, whether these drugs can be used any longer.
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PMID:Immune-type glomerulonephritis induced in the Brown-Norway rat with mercury-containing pharmaceutical products. 617 Sep 1

Changes in the fine structure of the glomerular filtration barrier were studied by perfusion of isolated rat kidneys with varying doses of protamine: 1) at low doses (110-150 micrograms/ml) ultrastructural changes were only detectable after prolonged recirculation (90-120'), 2) at high doses (250-330 micrograms/ml) profound epithelial foot process lesions were observed even after a short perfusion time, 3) at any concentration protamine particles were distributed in the laminae rarae of the GBM, thus visualizing neutralization of fixed negative charges. Reduction of glomerular anionic sites caused pronounced albuminuria even before podocyte morphological alterations were detectable. The effects of protamine on structure and function of the glomerular capillary wall are dose and time dependent. Besides intact morphology of the epithelial cells regular distribution of negative charges is necessary to maintain glomerular barrier function to macromolecules. Foot process alterations are not the primary reason for increased proteinuria but rather a secondary phenomenon.
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PMID:Glomerular albumin leakage and morphology after neutralization of polyanions. II. Discrepancy of protamine induced albuminuria and fine structure of the glomerular filtration barrier. 620 19

For a long time it was considered that immune complex nephritis was caused by the deposition of circulating immune complexes. The way these complexes penetrate into the GBM has not been satisfactorily explained. Recently, especially in the case of sub-epithelial immune complex deposits, an in situ formation has been discussed. Positively charged molecules have a marked affinity for the negatively charged GBM and can act as a target (planted antigen) for circulating antibody. Furthermore they can readily penetrate the GBM even when their size exceeds 500,000 daltons, whereas aniocatiocatiocationic molecules of over 70,000 daltons are effectively excluded. The interaction of chemically cationized proteins with the GBM is dependent on the size and charge of the molecule. Cationized IgG fixes to the GBM when its pI exceeds 9.0, ovalbumin only when its pI exceeds 10.0. Highly cationised proteins can be detected for several hours in the GBM. The reaction with antibody leads to the formation of sub-epithelial deposits which persist for weeks or even months in the GBM. Perfusion of microgram quantities of a highly cationised antigen directly into the left renal artery followed by the systemic injection of anti-body 1 h later is capable of inducing a typical ICGN with massive proteinuria. The above demonstrates that cationic proteins are nephritogenic antigens, which may also be involved in human glomerulonephritis.
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PMID:[A new concept for the pathogenesis of immune complex nephritis]. 621 67

Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.
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PMID:Detection of terminal complement components in experimental immune glomerular injury. 624 52

A proliferative glomerulonephritis was induced in rats preimmunised with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-rat GBM IgG. All the rats developed a severe proteinuria within 2-5 days after the injection of anti-GBM IgG. At the same time, many mononuclear phagocytes infiltrated the glomeruli, the colloidal iron staining of the glomerular filtration barrier was altered, and the urinary excretion of laminin and of neutral proteinase strongly increased. However, the pattern and intensity of staining of different collagenous and non-collagenous BM glycoproteins were not modified, as shown by indirect immunofluorescence microscopy. The existence of a direct significant correlation between the proteinuria and the laminin urinary excretion, and between the latter and the urinary neutral proteinase activity suggests that lysosomal proteinase of mononuclear phagocytes may be involved in the damage of the GBM during the course of this experimental glomerulonephritis.
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PMID:Studies on the glomerular filtration barrier and on the urinary excretion of basement membrane glycoproteins during the accelerated model of nephrotoxic serum nephritis. 636 61

Puromycin aminonucleoside (PA), injected intravenously into rats in a single dose, causes proteinuria and ultrastructural pathology reminiscent of human lipoid nephrosis (puromycin aminonucleoside nephrosis (PAN]. Glomerular epithelial cell (GEC) endocytosis was studied in this model and in rats with protein-overload proteinuria using ultrastructural morphometry. Disappearance curves were constructed for protamine-heparin aggregates (PHA), which localized in the subepithelial region of the glomerular basal lamina following intravenous injection of protamine followed by heparin. Five groups were studied: (a) preproteinuric PAN, 4 days after PA (mean 4.5 +/- 1.5 mg of urinary protein/24 hours); (b) proteinuric PAN, 10 days after PA (mean 128 +/- 9.6 mg/24 hours); (c) recovery from PAN (mean 12.5 +/- 1.5 mg/24 hours); (d) protein-overload proteinuria, induced by injecting albumin intraperitoneally (mean 211 +/- 15.9 mg/24 hours); and (e) saline-injected controls (mean 1.2 +/- 0.2 mg/24 hours). Only the proteinuric PAN animals (group 2) had altered GEC endocytosis with a PHA half-disappearance time different from the group 5 saline controls (143.2 versus 72.6 minutes, p less than 0.05). The half-disappearance times in groups 1, 3, and 4 were 74.6, 80.7 and 86.5 minutes, respectively. Altered GEC function was further characterized by comparing PHA disappearance with the abundance of albumin-filled vacuoles in the GEC. Prolongation of PHA disappearance in group 2 correlated with the virtual absence of vacuoles; they were abundant in nonproteinuric phases of PAN and in animals with overload proteinuria. We conclude (a) GEC endocytosis is reduced only during the proteinuric phase of PAN, (b) GEC endocytosis is active during the preproteinuric phase of PAN and is a factor that may account for the absence of protein in the urine despite abnormal GBM permeability, (c) decreased GEC endocytosis during proteinuric PAN reflects abnormal cell metabolism due to PA and is not simply a consequence of albuminuria, as overload proteinuria did not produce diminished PHA or albumin uptake.
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PMID:Inhibition of glomerular visceral epithelial cell endocytosis during nephrosis induced by puromycin aminonucleoside. 638 77

To obtain a better understanding of the mechanism of proteinuria in amyloidosis we investigated the ultrastructural distribution and pattern of arrangement of glomerular amyloid fibrils in 15 patients. Clinical data were correlated with the ultrastructural features and with the morphometric indices obtained from composite electron micrographs of whole glomeruli. The epithelial side of amyloid deposits showed spicules (discrete pointed bundles of fibrils) and apparent fraying which we termed tufts (ill-defined and diffuse expansion of fibrils). The extent of mesangial amyloid deposition and total GBM deposition did not correlate with proteinuria. Current data suggest the importance of partial detachment of epithelial cells in pathogenesis of proteinuria, which in turn correlates with distortion of amyloid fibrils, spicules and tufts.
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PMID:Proteinuria in amyloidosis correlates with epithelial detachment and distortion of amyloid fibrils. 647 58

The effects of steroids on the development of injury in two models of experimental glomerulonephritis (GN), (one mediated by neutrophils, the other by macrophages) were compared. The neutrophil-associated lesion [initiated by heterologous antiglomerular basement membrane (GBM) antibody] was characterized by the development of an exudative endocapillary GN with heavy neutrophil accumulation [mean, 6.9 neutrophils/glomerular cross section (N/GCS) +/- 2.9 SD], minor macrophage infiltration [7.9 macrophages/glomerulus (M/G) +/- 2.2 SD] and heavy proteinuria (1905 mg/24 hr +/- 520 SD). Steroid-treated (methylprednisolone, 2 mg/kg/12 hr i.v.) rabbits developed a marked monocytopenia, mild neutrophilia, and significant reduction in glomerular macrophage accumulation (0.3 M/G 0.02 SD). However, neutrophil accumulation (6.1 N/CGS +/- 2.5 SD), histological appearances, and proteinuria (1820 mg/hr +/- 490 SD) were unaffected. The macrophage-associated model of GN was induced by passive autologous rabbit anti-sheep IgG 15 hr after the injection of a subnephritogenic dose of the same anti-GBM antibody. The glomerular lesion was characterized by a diffuse endocapillary proliferative GN with heavy macrophage infiltration (54 M/G +/- 8 SD), insignificant neutrophil accumulation (0.8 N/GCS 0.02 SD), and the regular development of proteinuria (420 mg/24 hr +/- 80 SD). Steroid-treated rabbits developed a mild neutrophilia and a significant monocytopenia associated with abrogation of glomerular macrophage accumulation (2.3 M/G +/- 0.8 SD). This was associated with the prevention of the development of GN and proteinuria (22 +/- 9.5 SD). Thus, steroids produce monocytopenia and prevent glomerular macrophage accumulation and associated injury whereas neutrophil accumulation and injury is unaffected. These data suggest steroids may have widely varying effects on the outcome of leukocyte-associated experimental GN depending on the nature of the infiltrating cells.
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PMID:Differential effects of steroids on leukocyte-mediated glomerulonephritis in the rabbit. 650 35

The immunological and structural changes during the heterologous phase of experimental antibasement membrane antibody mediated disease was sequentially studied in the rat following single i.v. injections of rabbit antibodies to basement membrane antigens prepared from kidney, lung and salivary gland tissues. Although each of the anti-bodies bound strongly to GBM, structural changes were initially subtle accompanied by proteinuria and hematuria. More severe structural changes related to dose and duration of the disease did not appear for several weeks.
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PMID:Pathological changes in the heterologous phase of antibasement membrane antibody mediated disease in the rat. 672 33


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