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)

A postulated mechanism of immune glomerular injury is a direct interaction between antibody and glomerular epithelial cell (GEC) surface antigens. To explore this hypothesis, we examined the interaction of the noncomplement-fixing gamma 2-subclass of sheep anti-rat nephrotoxic serum (NTS), which causes immediate complement- and neutrophil-independent proteinuria in vivo, with rat GECs in culture. Reactivity of NTS with GEC surface antigens was determined by positive immunofluorescence of GEC plasma membranes and by the ability of NTS-coated tissue culture wells to provide an adhesive substrate for GECs. NTS immunoprecipitated two proteins (135 and 118 kDa) from surface-labeled GECs. Proteins of similar molecular mass were precipitated by a polyclonal rabbit antibody that identifies the beta 1-integrin chain of the mouse fibronectin receptor (anti-FnR). In addition, NTS identified similarly sized bands on Western blot analysis of cell membranes from isolated rat glomeruli. Similar reactivity was eluted from the glomeruli of proteinuric rats injected with NTS. NTS significantly inhibited GEC adhesion to laminin, types I and IV collagen, and fibronectin and prevented GEC spreading on types I and IV collagen. Anti-FnR similarly inhibited GEC adhesion. Cell viability was not affected. These results show that NTS recognizes a pair of GEC surface proteins that have the characteristics of an alpha- and beta 1-integrin and, at low concentrations, disrupt cell-matrix interactions.
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PMID:Nephrotoxic antiserum identifies a beta 1-integrin on rat glomerular epithelial cells. 137 74

In streptozotocin induced diabetes in rats, excretion of urinary protein fractions were studied in relation to structural changes in the renal glomeruli, using light and transmission electron microscopy. After six weeks of induced diabetes only beta 1 and beta 2 plasma globulins were significantly elevated. The amount of excreted proteins and degree of glomerular changes were not proportional. In the initial stages (1-2 weeks) glomerular structural changes were very mild and were accompanied by significantly elevated proteinuria. This progressed (4-8 weeks) to moderate to prominent structural changes with intermittent proteinuria except for the fractions beta 1 & beta 2 which were elevated throughout the duration of the experiment. The amount of proteinuria was not proportional to changes in the plasma protein levels. The following conclusions may be made: 1) The mild early glomerular abnormalities seem to be mainly due to acute metabolic disturbances. 2) An early indication of diabetic nephropathy is provided not only by albuminuria, but may also be an elevated excretion of beta-globulin fractions. 3) Decrease of albuminuria in the later stages of diabetes may be related to the deposition of albumin as a basement membrane-like material in the mesangium.
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PMID:Structural changes in glomeruli and proteinuria in streptozotocin diabetic rats. 252 Apr 52

In a 10-year retrospective study, we evaluated the clinicopathologic features and renal immunofluorescence patterns of glomerulonephritis in 41 dogs. On the basis of results of histologic examinations, the dogs were segregated into 3 groups, including membranous (n = 12), mesangioproliferative (n = 15), or membranoproliferative glomerulonephritis (n = 14). No significant differences existed among groups in regard to age or duration of illness. Most dogs had been ill for one month or longer. The proportion of dogs with azotemia, anemia, and hyperphosphatemia were not different among the disease groups. Proportion of dogs with hypoalbuminemia and the severity of hypoalbuminemia were not different among groups. Highest urine protein losses and 24-hour urine protein/creatinine ratios developed in dogs with membranous glomerulonephritis. Although hypoalbuminemia and hypercholesterolemia were common (49%), the formation of edema or ascites was not (15%) and, therefore, few dogs had all of the classic features of the nephrotic syndrome. Few dogs suffered thromboembolic complications. Antinuclear antibody titers developed in 11 dogs, the highest titers developing in dogs with polyarthritis and systemic lupus erythematosis. Cellulose acetate electrophoresis detected alpha 2 and beta 1 globulin spikes in most dogs (87%). Results of renal immunofluorescence testing were positive in 36 dogs, using polyvalent antisera for immunoglobulins (Ig)G, IgA, IgM, and/or antisera for complement factor C3. When monovalent antisera for IgG, IgA, and IgM, and fibrinogen were used, immunofluorescence was not observed as often. The major fluorescent pattern was discrete multifocal segmental granular glomerular fluorescence, consistent with immune-complex deposition. Two dogs had linear glomerular staining patterns; however, antibodies directed against normal glomerular basement membrane were not found via elution studies. A high prevalence of glucocorticoid excess (treatment with glucocorticoids and spontaneous hyperadrenocorticism) (34%), chronic inflammatory skin disease (27%), neoplasia (17%), polyarthritis (12%), and systemic lupus erythematosis (7%) were observed as clinical problems concurrent with glomerulonephritis. In 5 dogs, treatment of glomerulonephritis with prednisolone (0.5 to 1.1 mg/kg) did not result in beneficial effects and in fact appeared to be detrimental, leading to azotemia and worsening proteinuria and physical condition in some of the dogs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985). 354 34

In order to describe the outcome of a one-year material of hypertensive pregnancies, a retrospective analysis was made of the patients with respect to time of onset of hypertension, absence/presence of significant proteinuria, and maximum recorded serum urate values less or greater than 350 mumol/l. The material comprised 113 hypertensive patients, 3.7% of 3036 deliveries in 1980. Of these only 87 could be classified as intended. Twenty-two patients lacked information on serum urate values, and the remaining 4 did not fulfil the inclusion criteria. As the type of antihypertensive treatment was almost exclusively restricted to beta 1-selective betablockers, alone or in combination with hydralazine, the type of treatment given was analysed with respect to the classification system applied. From this retrospective study it is evident that most hypertensive patients tend to be older than the average pregnant woman and that they also tend to represent problems arising during recurrent pregnancies. Patients with additive risk factors such as proteinuria and high serum urate values tend to need more vigorous antihypertensive treatment and in that sense seem to be more difficult to treat. In our material, patients with an early rise in high blood pressure and high serum urate values accounted for the entire perinatal mortality of the hypertensive pregnancies. The values of serum urate monitoring and the future detection and monitoring of hypertensive pregnant patients is discussed.
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PMID:Risk grouping of 113 patients with hypertensive disorders during pregnancy, with respect to serum urate, proteinuria and time of onset of hypertension. 658 28

To study the role of lysosomal enzymes in glomeruli, we examined specific activities of lysosomal hydrolases in isolated glomeruli and, for comparison in isolated tubules, from rat kidney cortex of normal animals and animals with puromycin aminonucleoside nephrosis (PAN). Nephrotic syndrome was induced in rats by a single intraperitoneal injection of aminonucleoside and the rats were sacrificed at the time of peak proteinuria. Colloidal iron staining of renal cortex demonstrated decreased staining for the epithelial polyanion in animals with PAN. Lysosomal enzymes were determined by fluorogenic and colorimetric methods. In normal kidney, total specific activities of cathepsin beta 1, beta-2-fucosidase, acetyl-beta-glucosaminidase, and arylsulfatase were lower in glomeruli compared with tubules and with tissue slices of the same kidney. Total activity of acid phosphatase was higher in glomeruli than tubules. In glomeruli of PAN rats, there were lower activities of N-acetyl-beta-glucosaminidase, D-fucosidase, beta-glucosidase, beta-glucoronidase, and arylsulfatase compared with control rats. Activity of acid phosphatase, on the other hand, was higher in glomeruli of PAN than control rats. All differences were statistically significant. These studies demonstrate that (1) activities of lysosomal enzymes in normal glomeruli and in glomeruli of nephrotic rats have a property distinct from the rest of the kidney, and (2) the specific activities of lysosomal hydrolases are altered in glomeruli of rats with PAN. These studies suggest that changes in activities of lysosomal enzymes may be related to pathogenesis of this glomerulopathy.
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PMID:Activities of lysosomal enzymes in isolated glomeruli. Alterations in experimental nephrosis. 732 25

We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, respectively. Other prostaglandin synthesis was unaffected. Renal function such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation showed that bisoprolol significantly improved glomerular sclerosis by 29% and attenuated arterial damage by 71%, although tubular injury was not affected. The more severe the glomerulosclerotic lesions, the greater the generation of thromboxane and ET. The arterial lesions were positively correlated to thromboxane generation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alterations may be partly responsible for the amelioration of glomerular and arterial injury in Dahl S rats.
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PMID:Vasoconstrictors and renal protection induced by beta 1-selective adrenoceptor antagonist bisoprolol. 752 81

The present study was carried out to test whether transforming growth factor beta (TGF beta) plays a pathological role in the induction or progression of glomerulonephritis in a murine model of systemic lupus erythematosus (SLE), and whether dietary supplementation with fish oil (FO) can modulate the expression of TGF beta. Weanling female (NZB x NZW) F1 (B/W) mice were divided into three groups. One group was fed an unmanipulated diet (lab. chow; LC) and the other two groups were fed a nutritionally adequate semipurified diet supplemented with 10% CO or FO. Both water and food were provided ad libitum. Proteinuria and serum anti-dsDNA antibody levels were measured to assess disease progression. Mice were killed at 3.5 and 6.5 months of age and renal mRNA levels for TGF beta isoforms, fibronectin-1 (FN-1) and intercellular adhesion molecule-1 (ICAM-1) were studied by Northern blot analysis. TGF beta 1 protein levels were also examined in kidneys by Western blot analysis. Our results indicate that at 3.5 months of age, when urinary protein levels were undetectable and very low levels of anti-dsDNA were detected, no mRNA signal could be detected for TGF beta isoforms, ICAM-1 and FN-1 in either dietary group. However, at 6.5 months, the FO-fed mice, compared to LC and CO, had [1] greatly reduced proteinuria (LC: 2-3+, CO: 2-3+; FO: trace -1+) and serum anti-dsDNA antibodies; [2] improved survival (CO: 100% death (15/15) occurred by 8 months; FO: 50% were alive at 12 months (8/15) and [3] reduced renal TGF beta 1 mRNA and protein levels. TGF beta 2 and beta 3 were not significantly affected by FO diet. Similarly, lower levels of renal FN-1 and ICAM-1 mRNA were observed in FO fed mice. These data indicate that in B/W mice on a FO diet, prolonged survival and amelioration of renal disease may be attributed at least in part to lower levels of TGF beta 1 mRNA and protein in the kidneys.
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PMID:Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. 757 99

S-laminin/laminin beta 2, a homologue of the widely distributed laminin B1/beta 1 chain, is a major component of adult renal glomerular basement membrane (GBM). Immature GBM bears beta 1, which is replaced by beta 2 as development proceeds. In mutant mice that lack beta 2, the GBM remains rich in beta 1, suggesting that a feedback mechanism normally regulates GBM maturation. The beta 2-deficient GBM is structurally intact and contains normal complements of several collagenous and noncollagenous glycoproteins. However, mutant mice develop massive proteinuria due to failure of the glomerular filtration barrier. These results support the idea that laminin beta chains are functionally distinct although they assemble to form similar structures. Laminin beta 2-deficient mice may provide a model for human congenital or idiopathic nephrotic syndromes.
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PMID:The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. 767 Apr 89

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

We have previously shown beneficial effects of dietary protein restriction on transforming growth factor beta (TGF-beta) expression and glomerular matrix accumulation in experimental glomerulonephritis. We hypothesized that these effects result from restriction of dietary L-arginine intake. Arginine is a precursor for three pathways, the products of which are involved in tissue injury and repair: nitric oxide, an effector molecule in inflammatory and immunological tissue injury; polyamines, which are required for DNA synthesis and cell growth; and proline, which is required for collagen production. Rats were fed six isocaloric diets differing in L-arginine and/or total protein content, starting immediately after induction of glomerulonephritis by injection of an antibody reactive to glomerular mesangial cells. Mesangial cell lysis and monocyte/macrophage infiltration did not differ with diet. However, restriction of dietary L-arginine intake, even when total protein intake was normal, resulted in decreased proteinuria, decreased expression of TGF-beta 1 mRNA and TGF-beta 1 protein, and decreased production and deposition of matrix components. L-Arginine, but not D-arginine, supplementation to low protein diets reversed these effects. These results implicate arginine as a key component in the beneficial effects of low protein diet.
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PMID:L-arginine may mediate the therapeutic effects of low protein diets. 775 41


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