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)

The time course of Heymann's nephritis (HN), assessed on proteinuria and immunomorphology, has been compared in Lewis (LEW) rats immunized with BB alone (group A) or injected with HgCl2 and subsequently immunized in a similar manner (group B). Whereas all rats from group A developed typical HN characterized by heavy proteinuria and abundant glomerular immune deposits, rats from group B did not develop or developed a markedly attenuated form of HN; proteinuria was never detectable, immune deposits were absent or minimal. No abnormalities were found in rats injected with HgCl2 alone. In order to explain our findings, we have studied the glomerular and tubular expression of the 330 kD nephritogenic glycoprotein (gp330) as well as the corresponding antibody response. In rats receiving HgCl2, gp330 was normally expressed on BB and glomerular epithelial cells as indicated by in vitro and in vivo binding of anti-gp330 antibodies, but titers of anti-BB and anti-gp330 antibodies were considerably lower than in group A control rats. These findings therefore suggest that HgCl2 acts by its immunodepressive effect recently related to an increase in T suppressor cells. This effect is paradoxical since HgCl2 induces autoimmunity in Brown-Norway rats, and we suggest that it may be akin to observations reported in clinical practice where drugs may be immunostimulatory in some patients and immunodepressive in others. The mercury model may therefore represent a unique tool to evaluate the relationship between genetics and drug-induced immune dysregulation.
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PMID:Down modulation of Heymann's nephritis by mercuric chloride. 349 56

The effect of prostaglandin E1 on mercury-induced autoimmune disease in brown Norway rats has been investigated. Daily doses of 6 to 24 micrograms prolonged survival and significantly decreased proteinuria, deposition of immune reactants in the glomeruli, circulating anti-glomerular membrane antibody production, total serum IgE, and circulating immune complex level. A dose of 3 micrograms was also effective but to a lesser degree. These results show the efficiency of prostaglandin E1 in yet another autoimmune disease, show that the beneficial effect of prostaglandin E1 in this model is related to its immunosuppressive effects, and suggest that modification of prostaglandin-mediated suppression induced by HgCl2 might play a role in the pathogenesis of this autoimmune disease.
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PMID:Effect of prostaglandin E1 in brown Norway rats with mercury-induced autoimmune disease. 352 21

Anti-laminin antibodies were sought for in the serum of workers exposed to mercury vapour (Hg, n = 58), lead (Pb, n = 38) or cadmium (Cd, n = 47). Thirty-one workers removed from Cd exposure for an average of eight years were also examined. Compared with control workers matched for age and socio-economic status, the prevalence of circulating anti-laminin antibodies was not increased in workers exposed to Hg (mean duration of exposure: 7.9 years and mean urinary excretion of Hg: 72 micrograms/g creatinine) nor in those exposed to Pb (mean duration of exposure: 10.6 years and mean Pb levels in blood: 535 micrograms/l). In contrast, anti-laminin antibodies were significantly more prevalent in Cd-exposed workers whose urinary Cd exceeded 20 micrograms/g creatinine. This observation was made in both currently exposed workers and in workers removed from Cd exposure (mean duration of exposure: 9.4 and 24.6 years and mean urinary Cd: 7.8 and 13.4 micrograms/g creatinine respectively). These autoantibodies were found in Cd workers with normal renal function as well as in those with increased proteinuria.
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PMID:Search for anti-laminin antibodies in the serum of workers exposed to cadmium, mercury vapour or lead. 357 Apr 94

An attempt was made to develop a model of chronic renal disease in the rat through repeated administration of a nephrotoxin specific for proximal tubular epithelium. Mercuric chloride was administered by subcutaneous injection in gradually increasing amounts over a period of 21 weeks. The dose ranged from 1.125 mg/kg once a week to 2.0 mg/kg twice a week. Measured parameters of renal function include plasma urea nitrogen, plasma creatinine, 24-hour urine output volume, and 24-hour urinary protein excretion. When compared to their own pretreatment values and those of the age/weight-matched control animals, the mercuric chloride-treated rats exhibited no significant abnormalities in these parameters of kidney function with the exception of a mild proteinuria at 21 weeks. Light microscopic examination of the kidneys of the mercury-treated rats revealed mild tubular, interstitial, and glomerular lesions which were significantly worse than those in the kidneys of the controls. This study demonstrates the ability of the kidney to sustain a considerable degree of resistance to inorganic mercury toxicity when exposure is continuous over a prolonged period of time. It also demonstrates the inability of commonly measured clinical laboratory parameters of kidney function to identify the effects of chronic mercuric chloride toxicity in the rat.
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PMID:Renal resistance to mercuric chloride toxicity during prolonged exposure in rats. 375 Aug 10

A low dose of methyl mercuric chloride fed to female rats for 12 weeks caused extrusion of numerous cytoplasmic masses from kidney proximal tubule cells of the pars recta segment. These masses were characterized ultrastructurally by the presence of a smooth endoplasmic reticulum aggregate. The in vivo metabolism of methyl mercury to inorganic mercury may produce this effect and account for the proteinuria observed in persons occupationally exposed to organic mercury compounds.
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PMID:Ultrastructural evidence for nephropathy induced by long-term exposure tosmall amounts of methyl mercury. 505 18

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

Chronic mercuric chloride intoxication in an aged horse given 0.8 mg Hg/kg/day for 14 weeks was manifest by signs of progressive respiratory difficulty and renal disease. The effects were not self-limiting after mercury was withdrawn, and the animal was destroyed six weeks later. Renal function changes included heavy glycosuria, modest proteinuria, phosphaturia, reduced urine osmolality, gradually increasing urine production, reduced glomerular filtration rate, and terminally, azotemia. The condition bore similarities to the Fanconi syndrome in man. Urinary gamma-glutamyl transpeptidase, alkaline phosphatase and amino-aspartate transferase activities were inconsistent indicators of tubular damage in random samples at this dose rate. The pathologic response was characterized by extensive granulomatous infiltration throughout the lungs, in particular, and to a lesser extent in the kidneys, liver and bone marrow. The renal changes included this marked interstitial reaction and proximal tubular degeneration. Mercury levels were negligible in the lungs and highest in the renal cortex. The granulomatous reaction was not encountered in previous mercury toxicity studies in horses and may indicate an individual sensitivity to the agent.
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PMID:Some effects of chronic mercuric chloride intoxication on renal function in a horse. 621 26

The first two cases outlined above with intractable massive proteinuria and uremia, were followed and treated with standard medical therapy and dialysis. After a period of study and demonstration of clinical deterioration both patients were given solutions containing sodium mercaptomerin. Within days there was a decline in urine protein excretion and a variable increase in serum protein concentration. The patients demonstrated an increase in blood pressure, which made hemodialysis treatment possible. No deleterious effects from the mercury salts were noted. These observations suggest that in selected cases nephrotoxic agents may be of value in decreasing massive proteinuria, and improving protein homeostasis in uremic patients. The ideal agent should be non-toxic to other organs and produce selective renal ablation (15). Although mercury is not the ideal agent, in these cases it did not produce observable side effects. This new method, applicable to dialysis patients with massive proteinuria, and of help in the control of uncontrollable hypertension in uremia, is an interesting new approach for our therapeutic armamentarium.
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PMID:Medical nephrectomy: the use of metallic salts for treatment of end stage massive proteinuria and renal hypertension. 633 53

The renal function of a population of workers occupationally exposed to mercury in the chlor-alkali industry has been examined and compared to that of a population of workers with no occupational exposure to mercury. Measurement of specific urinary proteins and enzymes have been carried out on each individual on three separate occasions and have been complemented by blood plasma measurements at the final visit. Under the conditions of exposure to mercury sustained in this study, there is no evidence of an increased prevalence of renal dysfunction as indicated by enzyme and protein measurements. The urinary concentration of the low molecular weight protein, beta 2-microglobulin, is significantly lower in the mercury-exposed group than in the control group. In contrast to recently published literature, no relationship is seen between urinary mercury concentration and the appearance of high molecular weight protein in urine. A small increase in the prevalence of higher activities of the urinary enzyme N-acetyl-beta-glucosaminidase and gamma glutamyl transferase is observed when the urinary mercury concentration exceeds 100 micrograms/g creatinine. A small increase in the prevalence of raised urinary N-acetyl-beta-glucosaminidase activity is observed when the duration of exposure to mercury exceeds ten years. The pattern of proteinuria has been characterised in a total of sixteen individuals from both populations; a low molecular weight proteinuria is seen in three individuals from the control group whilst a high molecular weight proteinuria is seen in the remainder (seven in the control and six in the mercury group).
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PMID:An evaluation of renal function in workers occupationally exposed to mercury vapour. 635 40

The combined use of ultrastructural morphometry and X-ray microanalysis in conjunction with biochemical analysis is one approach to elucidating mechanisms of metal nephrotoxicity at the cellular level. Ultrastructural morphometry conducted on proximal tubule cells of rats exposed to low levels of methyl mercury for prolonged periods of time showed statistically significant increases in the volume densities of the lysosomal and mitochondrial compartments. These findings were associated with marked changes in lysosomal marker enzymes and mitochondrial heme biosynthesis enzymes leading to the detection of a renal porphyrinuria that occurred before changes in standard tests of renal function. Ultrastructural morphometry, X-ray microanalysis, and biochemical studies of the low-molecular-weight tubular proteinuria produced by injection of cadmium metallothionein (CdMT) showed a rapid proximal tubule cell lysosome uptake and degradation of the CdMT complex, which led to a subsequent decrease in the numerical density (Nv) and average diameter of lysosomes and to an increase in the Nv of apical pinocytolic vesicles with time. The data indicate disruption of the normal primary lysosome-pinocytolic vesicle fusion process and related development of tubular proteinuria. Ultrastructural techniques may provide information useful in elucidating mechanisms of ongoing metal-induced nephrotoxic processes when consideration is given to sampling strategies for morphometric analysis and the inherent detection limits, elemental volatility, translocation effects, and limitations of quantification for X-ray microanalysis in soft biological tissues.
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PMID:Role of ultrastructural techniques in understanding mechanisms of metal-induced nephrotoxicity. 661 93


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