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Query: UMLS:C0033687 (proteinuria)
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Exposure to cadmium can give rise to a number of adverse health effects. In human risk assessment it is important to identify effects that occur at relatively low exposures, i.e., the critical effects, which are crucial for preventive action. The effect of cadmium on the kidney, namely, tubular dysfunction, has been regarded as the critical effect in long-term human exposures. Quantitative dose-response data can be derived from a risk model based on metabolic parameters and observed relationships between cadmium concentrations in the renal cortex and the occurrence of proteinuria in industrial workers. There is reasonable agreement between this model and epidemiological observations. Low-dose-low-incidence extrapolations have been made based on this model. However, experimental and epidemiological studies are providing increasing evidence that cadmium is carcinogenic and this serious effect, considered to be stochastic in character, may reasonably be considered as a critical effect. A quantitative evaluation is difficult with the available data. The preventive action usually taken for substances which are considered to be carcinogenic is to limit the use of and exposure to cadmium as much as possible, thus achieving exposure levels for cadmium lower than those giving rise to kidney damage.
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PMID:Application of the 'critical effect' and 'critical concentration' concept to human risk assessment for cadmium. 130 55

The critical levels for monitoring cadmium health effects in 358 workers engaged in ore crushing/roasting (cadmium concentration in the workplace air 2.5-6.5 mg/m3), dry smelting (10.8-23.3 mg/m3), cadmium melting (0.01-0.16 mg/m3), and ingot making (2.8-4.7 mg/m3), were investigated. Exposure parameters such as blood and urinary cadmium were determined, together with biological parameters such as proteinuria, amino acids, glucose, beta 2-microglobulin, retinol-binding protein, albumin, plasma beta 2-microglobulin, creatinine clearance, tubular reabsorption of beta 2-microglobulin and phosphate, and blood and urinary levels of zinc, copper and lead. Factor analysis and stepwise regression analysis were then applied to the data to classify parameters and to find the main contributing parameter. Blood and urinary cadmium, urinary beta 2-microglobulin, retinol-binding protein and the ratio of urinary beta 2-microglobulin to albumin were also subjected to multiple correlation analysis, multiple regression analysis and the Chi-square test was applied to contingency tables. It is concluded, based on the data, that cadmium health effects may be assessed by using the following critical levels: blood cadmium: 10 micrograms/l, urinary cadmium: 10 micrograms/g creatinine; urinary beta 2-microglobulin: 2000 micrograms/g creatinine, urinary retinol-binding protein: 200 micrograms/g creatinine and a ratio of urinary beta 2-microglobulin to albumin of 0.001.
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PMID:Critical levels of blood and urinary cadmium, urinary beta 2-microglobulin and retinol-binding protein for monitoring cadmium health effects. 130 59

The assessment of acceptable exposure levels to cadmium in the work or general environment frequently relies on the analysis of the relationships between urinary cadmium (an indicator of the body burden) and proteins used as markers of nephrotoxicity. A possibility which cannot be excluded a priori is that the relationships between cadmium and proteins in urine might sometimes result from renal dysfunction unrelated to cadmium toxicity. To test this hypothesis, we have measured cadmium in the urine of 114 pregnant women of whom about 20% had developed a reversible tubular proteinuria. Cadmium excretion was correlated significantly with age but not with duration of pregnancy nor with low molecular weight urinary proteins. This indicates that tubular dysfunction unrelated to cadmium exposure does not necessarily increase cadmium excretion. Hence, these data support the conclusion of the recent Cadmibel Study on the renal tubular effects of cadmium on the general population of Belgium.
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PMID:Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study. 130 60

Statutory health surveillance of occupational exposure to cadmium exists in most Western countries. For biological monitoring, both indicators of internal dose and indicators of effect are available. Cadmium in urine is an indicator of chronic exposure and essentially reflects the body burden under low-exposure conditions and in the absence of renal damage. Whole blood cadmium is primarily a useful indicator for use in evaluations of recent exposures. Biological threshold limit values for cadmium in urine and blood are based on the correlation of biological levels with thresholds for renal dysfunction. The use of markers of high and low molecular weight proteinuria should be integrated into the health surveillance of cadmium-exposed workers. Priority should be given to the determination of albumin and of proteins such as beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin. Interpretation of biological monitoring data in terms of the threshold values requires a programme of periodic biological, medical and environmental monitoring.
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PMID:Biological monitoring in the occupational setting--relationship to cadmium exposure. 130 73

One group of male Wistar rats (Group B) was pretreated by a daily subcutaneous injection with CdCl2 during 5 days with increasing doses (0.5, 1, 1, 2 and 2 mg Cd/kg). Another group of rats (Group A) was daily given normal saline subcutaneously for 5 days. On the second day after the last injection, a single s.c. injection of 109Cd-metallothionein (CdMT, 0.4 mg Cd/kg) was given to each animal in both groups. Urinary calcium, protein, metallothionein (MT), N-acetyl-beta-D-glucosaminidase (NAG) and gamma glutamyltransferase (gamma-GT) were measured. In Group A, calciuria, proteinuria, metallothioneinuria and enzymuria was induced by CdMT. Calciuria reached a peak during 0-6 h after the administration of CdMT, thus appearing earlier than other effects. Enzymuria was displayed at 6-12 h for gamma-GT and 12-24 h for NAG. A prominent increase of proteinuria appeared at 24-48 h after the challenge of CdMT. In Group B, no significant increase of urinary calcium, protein, or NAG was observed after the CdMT injection and urinary gamma-GT was only slightly elevated, thus demonstrating the protective action of pretreatment. This study demonstrates for the first time that calciuria, one of the signs of cadmium nephrotoxicity, can be prevented by cadmium pretreatment. Urinary MT increased slightly during the 4-5 days of CdCl2 pretreatment. This is in accordance with previous observations that cadmium pretreatment induces new synthesis of MT which is likely to constitute the background for the resistance to the CdMT challenge to the kidney.
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PMID:Modulation of calciuria by cadmium pretreatment in rats with cadmium-metallothionein-induced nephrotoxicity. 136 Jul 15

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.
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PMID:Exogenous metallothionein and renal toxicity of cadmium and mercury in rats. 147 92

A 3-year-old boy with mixed glomerular/tubular proteinuria, mental retardation, and hyperkinesis is described. The proteinuria was discovered at the age of 3 years on urinary mass screening. Most of the urinary protein consisted of albumin, accompanied by increases in low molecular weight proteins, including beta 2-microglobulin and alpha 1-microglobulin. Mixed glomerular/tubular proteinuria is known to be caused by the following conditions: chronic renal failure, chronic pyelonephritis, cadmium poisoning, tubulointerstitial nephritis of various etiologies, and after strenuous, short-term, exhaustive exercise. The present patient did not display any of these disorders or conditions.
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PMID:Glomerular/tubular mixed-type proteinuria in a 3-year-old boy with mental retardation and hyperkinesis. 147 31

The relationship between proteinuria and glomerular polyanion (GPA) charge has been studied in a model of experimental cadmium (Cd) nephropathy. Female Sprague-Dawley rats were administered Cd in drinking water for up to 18 months. From month 2, the animals showed an elevation of albuminuria preceding by about 6 months the rise of urinary beta 2-microglobulin and IgG. The nephrotoxic action of Cd was not readily detectable on the basis of the urinary output of beta-N-acetylglucosaminidase, alanine aminopeptidase and lactate dehydrogenase. These enzymes showed either little variation or were affected late in the intoxication process. Administration of Cd for 12 or 18 months did not impair the GFR. The glomerular origin of the albuminuria induced by Cd was demonstrated by estimating the glomerular filtration of rat or human (injected intravenously) albumin in rats whose tubular reabsorption had been blocked by a saturating dose of cytochrome C. The GPA charge was assessed by measuring the binding of the cationic dye, Alcian blue (AB), to membranes of isolated glomeruli. The sialic and sulfate content of these membranes was also determined. The Cd induced-albuminuria was negatively correlated (r = -0.73; n = 37) with the AB binding to glomerular membranes, their sialic acid content (r = -0.39) but not with their sulfate content (r = -0.15). A negative correlation (r = -0.62; n = 37) was also observed between the albuminuria and red blood cell membrane negative charges largely contributed by sialic acid. All these observations can be interpreted as the evidence that Cd enhances the glomerular filtration of proteins through a GPA depletion involving mainly sialic acid.
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PMID:Loss of glomerular polyanion correlated with albuminuria in experimental cadmium nephropathy. 151 26

Disorders of olfaction affect millions of Americans, but the extent to which occupational and environmental exposures contribute to these disorders is unknown. We examined 55 workers with chronic occupational exposure to cadmium fumes in a brazing operation. We estimated cadmium body burden using urinary cadmium levels and assessed cadmium-induced renal damage by urinary beta 2-microglobulin levels. We quantified olfactory function using a standardized test that measured two components of olfaction, butanol detection threshold and odor identification, and compared workers with a reference group. Forty-four percent of the cadmium-exposed workers were mildly hyposmic, and 13% were either moderately or severely hyposmic. In the reference group, 31% were mildly hyposmic, and the rest were normosmic. The workers with both high urinary cadmium levels and tubular proteinuria had the most significant olfactory dysfunction, with a selective defect in odor detection threshold. Our findings suggest that chronic occupational cadmium exposure sufficient to cause renal damage also is associated with impairment in olfactory function.
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PMID:Olfactory impairment after chronic occupational cadmium exposure. 161 90

The U.S. Occupational Safety and Health Administration (OSHA) has proposed a revised 8-hour permissible exposure limit (PEL) for cadmium in air of either 1 or 5 micrograms/m3, based upon the prevention of lung cancer and kidney dysfunction. To evaluate the scientific basis for these alternative standards, we compare the OSHA estimates of risk, derived from mathematical modelling of selected studies, to empirical data on lung cancer and kidney dysfunction in the published literature. At least seven epidemiologic studies examine renal tubular proteinuria by cumulative cadmium exposure. Three suggest increased proteinuria at cumulative exposures below 500 micrograms/m3-year (equivalent to a PEL of 11.1 micrograms/m3 over 45 working years). One shows prevalence increasing at cumulative exposures between 100 and 299 micrograms/m3 (equivalent to a PEL between 2.2 and 6.6 micrograms/m3). Insufficient data exist to estimate a no-effect level for kidney toxicity. For lung cancer, qualitative evidence of carcinogenicity in humans is seen in four of five occupational cohorts. Quantitative estimates of risk based on epidemiologic data provide lower and more plausible estimates of lifetime risk than do estimates from a rodent bioassay. The data overall suggest that the PEL for cadmium should not exceed 5 micrograms/m3 to protect workers from kidney dysfunction and lung cancer over a working lifetime.
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PMID:Scientific basis for an occupational standard for cadmium. 179 11


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