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)

Total proteinuria (biuret method) and the urinary excretion of specific proteins (albumin, transferrin, orosomucoid and IgG measured by an automated immunoprecipitin reaction and beta 2-microglobulin determined by radioimmunoassay) have been assessed in four groups of workers: a control group (n = 88) and a group exposed to cadmium (n = 148), mercury vapour (n = 63) and lead (n = 25) respectively. The results demonstrate that a moderate exposure to lead (lead concentration in blood < 62 micrograms/100 ml) does not change the prevalence of renal dysfunction, whereas mercury vapour exposure increases the prevalence of subjects with excessive excretion of albumin (> 12 mg/g creatinine), orosomucoid (> 4.35 mg/g creat.) and IgG (> 3.5 mg/g creat.). Besides an increased excretion of beta 2-microglobulin (> 200 micrograms/g creat.) workers exposed to cadmium excrete a greater amount of high molecular weight proteins. An increased excretion of urinary proteins occurs when mercury and cadmium level in urine exceeds 50 and 10 micrograms/g creatinine respectively.
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PMID:Relationship between exposure to heavy metals and prevalence of renal dysfunction. 693 5

The nephrotoxicity associated with mercury may be manifested as either acute tubular necrosis or an immune complex glomerulonephritis, depending upon the conditions under which the patient is exposed to the metal. Two patients with industrial exposure to mercury developed the nephrotic syndrome due to membranous glomerulonephritis. A multidisciplinary approach was used to define more precisely the pathogenetic mechanisms involved in the production of the glomerular lesion. Although glomeruli were normal by light microscopy, immunohistochemical studies demonstrated confluent finely granular epimembranous deposits of IgG and C3. This distribution was confirmed at the ultrastructural level with immunoelectron microscopy. High resolution elemental analysis of electron dense inclusions in tubular epithelial phagolysosomes demonstrated energy dispersion spectra characteristic of coexisting mercury and selenium. Eluates from the biopsy material were not immunoreactive against normal rat or human kidney. There was no immunoreactivity of epimembranous deposits with antibodies having renal tubular epithelial antigen or urinary uromucoid specificity. These observations suggest that a distinctive immunopathologic lesion is associated with mercury-associated membraneous glomerulonephritis, that the role of the metal itself may only be coincidental, and that the involved antigen remains unknown. Prednisone therapy had no documented persistent beneficial influence upon the level of proteinuria in one patient who has been lost to follow-up. In one patient not treated with steroid therapy, withdrawal of exposure to the metal resulted in disappearance of mercury from body fluids and clinical remission.
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PMID:Membranous glomerulonephritis associated with industrial mercury exposure. Study of pathogenetic mechanisms. 704 18

Renal function and psychomotor performance (eye-hand coordination, arm-hand steadiness) of a group of 43 workers exposed to mercury vapor were examined. Their mean age an average duration of exposure to mercury were 38 and 5 years, respectively. The results were compared with those in a matched group of 47 control workers. Increased proteinuria and albuminuria were found slightly more prevalent in the Hg-exposed group than in the control workers. These results are in agreement with those found during a previous study carrier out in another group of workers also exposed to elemental mercury (Buchet et al. 1980). The scores of the psychomotor tests were less satisfactory in the Hg workers than in the control workers, the arm-hand steadiness test being more discriminative than the eye-hand coordination test. Preclinical changes in psychomotor function can be detected independently of the presence of signs of renal dysfunction. No clear-cut relationships were found between the prevalence of abnormal psychomotor scores and the level of mercury in blood (HgB) or in urine (HgU). Increased prevalences of abnormal psychomotor scores seem however to occur for HgB between 1 and 2 micrograms/100 and for HgU between 50 and 100 micrograms/g creatinine. Therefore, a biologic threshold limit value of 50 micrograms/g creatinine in proposed for urinary mercury to prevent the development of preclinical effects on the central nervous system. A similar critical HgU level based on renal dysfunction prevalences has been suggested in a previous study.
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PMID:Comparison of renal function and psychomotor performance in workers exposed to elemental mercury. 708 88

The purpose of the present study was to determine whether lysosomal accumulation of mercury in the kidney is due to a leakage of protein-bound mercury through the glomerular filtration barrier followed by reabsorption into the lysosomal system of the proximal tubule. The subcellular distribution of mercury in the kidney was studied in four different groups of rats with and without proteinuria: normal young rats, young rats with aminonucleoside nephrosis, old rats with spontaneous proteinuria, and old rats with chronic mercury intoxication and proteinuria. Radioactive mercuric chloride (203HgCl2) was injected s.c. into the rats 72 hours before sacrifice. Cell fractionation experiments were carried out on homogenates of the renal cortex by differential centrifugation. Determination of radioactive mercury in the subcellular fractions revealed that mercury was concentrated in the lysosomal fraction of all rats with proteinuria. In contrast, normal rats without proteinuria had the highest concentration of mercury in the supernatant, and there was no enrichment of mercury in the lysosomal fraction. Gel filtration chromatography performed on urine samples from proteinuric rats demonstrated that excreted mercury in renal lysosomes of proteinuric urine support the hypothesis that mercury bound to plasma proteins passes the glomerular filtration barrier in proteinuric conditions and enters the lysosomal system of the proximal tubule by way of endocytosis.
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PMID:Mercury accumulation in kidney lysosomes or proteinuric rats. 723 Jun 9

The nephrotic syndrome, characterized by nonselective proteinuria, hypoproteinemia, hypoalbuminemia, and ascites, was observed in a 10-month-old male cat. Profound glomerular changes and renal tubular changes appear to have been induced by iatrogenic chronic exposure to metallic mercury originally contained in a rectal thermometer. Large concentrations of mercury were present in the kidneys, liver, spleen, and urine. Evaluation of glomeruli by immunofluorescent microscopy revealed interrupted granular deposition of immuno-globulin G and the third component of complement in glomerular capillary walls and the mesangium. Electron microscopic evaluation of glomeruli revealed diffuse alterations in glomerular basement membranes and visceral epithelial cells. Small electron dense deposits were observed in capillary walls, but they were not characteristic of immune complexes. The mechanism(s) responsible for the mercury induced glomerulonephropathy in this patient could not be determined on the basis of available data.
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PMID:Membranous glomerulonephropathy and nephrotic syndrome associated with iatrogenic metallic mercury poisoning in a cat. 725 62

The subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury-induced membranous nephropathy consist of autoantibodies directed to laminin P1 and of complement. The animals develop massive proteinuria within 10-14 days which is associated with obliteration of foot processes of glomerular visceral epithelial cells (GVEC), or podocytes. Previous studies indicate that these autoantibodies are probably not the sole mediator of proteinuria and GVEC damage. In this study we investigated whether circulating or macrophage-derived cytokines can contribute to the GVEC changes as detected in vivo. In vivo at the height of the proteinuria, increased intraglomerular IFN-gamma immunoreactivity was found. In diseased rats a five-fold increase in intraglomerular macrophages was found, but we could not detect intraglomerular IFN-alpha, IFN-beta, IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) by using immunohistology. Subsequently, we exposed cultured GVEC to these cytokines to investigate their cytotoxic effects on several physiological and structural parameters. IFN-gamma and IL-4 were the only cytokines that exerted toxic effects, resulting in a rapidly decreased transepithelial resistance of confluent monolayers, which was closely associated with altered immunoreactivity of the tight junction protein ZO-1. IL-4 also affected vimentin and laminin immunoreactivity. IFN-gamma and IL-4 only interfered with monolayer integrity when added to the basolateral side of the GVEC, indicating specific (receptor-mediated) effects. Only IL-4 decreased the viability of the cells, and treated monolayers demonstrated an increased passage of the 44-kD protein horseradish peroxidase. From our experiments we concluded that IFN-gamma subtly affected monolayer integrity at the level of the tight junctions, and that IL-4 additionally induced cell death. We hypothesize that the toxic effects of the cytokines IFN-gamma and IL-4 as seen with cultured podocytes are necessary together with the autoantibodies, for the ultimate induction of proteinuria in mercury nephropathy in the DZB rat.
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PMID:Interferon-gamma (IFN-gamma) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes. 758 70

Chronic exposure to inorganic mercury can cause kidney injury. Evidence gained from occupational medicine indicates that individuals who are exposed to only environmental sources, including amalgam tooth fillings, are at very little risk. Animal experiments, however, have revealed glomerular lesions of immunologic origin after low-dose exposure to inorganic mercury. In this study, the association between the number of amalgam tooth surfaces, urinary mercury, and proteinuria was explored in a sample of 48 randomly selected, apparently healthy male students who were 17-22 y of age. Presence of any of the following proteins in two separate urine samples was considered to be potentially indicative of any tubular and/or glomerular lesion: albumin, alpha-1-microglobulin (HC-protein), kappa and lambda light chains, and N-acetyl-beta-D-glucosaminidase. No significant relationship was found between any of the proteins and amalgam or urinary mercury. The results of this study did not suggest that amalgam fillings cause kidney dysfunction in humans.
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PMID:Dental amalgam, low-dose exposure to mercury, and urinary proteins in young Swedish men. 778 45

The activity of beta-N-acetylglucosaminidase (beta-NAG) was determined in 41 workers of a chemical plant, exposed to metallic mercury, and in 10 controls. In addition, a routine urine examination was performed and the level of creatinine was measured in serum. The mercury excretion in urine in the exposed workers exceeded admissible biological concentrations three times, on average. In the group exposed to mercury the beta-NAG activity in urine was significantly higher than in the a control group. Several cases of trace proteinuria and microscopic haematuria were found in the exposed group. A mean beta-NAG activity in urine was significantly higher in those cases than in other persons. The study proved the usefulness of determinations of the beta-NAG activity in urine in assessing nephrotoxicity in workers exposed to metallic mercury.
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PMID:[Beta-n-acetylglucosaminidase in urine as a sign of kidney damage in workers exposed to metallic mercury]. 800 20

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

Repeated exposure to relatively low doses of mercuric chloride causes a variety of autoimmune responses in rats of the Brown Norway (BN) strain. These animals experience a membranous glomerulonephritis, characterized by the production of autoantibodies to renal antigens (e.g., laminin) and proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury. Despite extensive investigations, the mechanisms of immunoregulation in this animal model are still unknown. RT6+ T lymphocytes may have a regulatory role in both BN and LEW rats. This hypothesis is suggested by our finding of a mercury-associated decrease of RT6+ T cells in lymph nodes of BN rats exposed to mercury and the lack of such effect in similarly treated LEW rats. In the present report we show that congenic LEW.1N or BN.1L had no renal autoimmune disease after treatment with HgCl2. FCM analysis of mercury-treated LEW.1N revealed that RT6.1+ T lymphocytes were significantly decreased in both spleen and lymph nodes of these animals. Experimental depletion of RT6+ T cells (by monoclonal antibody treatment or gamma irradiation) in LEW.1N and BN.1L rats did not favor the induction of renal autoimmunity after exposure to mercury. On the other hand, BN-->LEW.1N chimeras (obtained by adoptive transfer of BN lymphocytes into gamma-irradiated LEW.1N rats) experienced autoimmune responses to kidney antigens when treated with HgCl2. They had autoantibodies to laminin and linear binding of immunoglobulins in their kidneys as well as a decreased percentage of RT6.2+ T lymphocytes in cervical lymph nodes. Therefore, the different components of this experimental model can now be dissected using various types of BN-->LEW.1N chimeras, obtained by the adoptive transfer of purified T cell subsets.
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PMID:Mercury-induced renal autoimmunity in BN-->LEW.1N chimeric rats. 816 52


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