Urinary cadmium

Kubaslk, N. P. and Volosln, M. T. "A Simplified Determination of Urinary Cadmium, Lead, and Thallium, with Use of Carbon Rod Atomization and Atomic Absorption Spectrophotometry . Clin. Chem. (1973), 19, 954-958. 

A negative correlation was found between PbB and systolic pressure in Belgian men in the Cadmibel study (a cross-sectional population study of the health effects of environmental exposure to cadmium) (Staessen et al. 1991). In this study, blood pressure and urinary cation (positive ions found in the urine, such as sodium, potassium, and calcium) concentration data were obtained from 963 men and 1,019 women multiple stepwise regression analyses were conducted adjusting for age, body mass index, pulse... 

Roels HA, Lauwerys RR, Buchet J-P. 1990. Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapor. Br J Ind Med 47 331-337. 

A number of workers have described methods for the determination of mercury in which the mercury is first reduced to the element or collected as the sulfide on a cadmium sulfide pad. It is then volatilized into a chamber for measurement. These techniques are extremely sensitive. Thillez108) recently described a procedure for urinary mercury in which the mercury is collected on platinum and then volatilized into an air stream. Rathje109) treated 2 ml of urine with 5 ml of nitric acid for 3 min, diluted to 50 ml, and added stannuous chloride to reduce the mercury to the element. A drop of Antifoam 60 was added and nitrogen was blown through the solution to carry the mercury vapor into a quartz end cell where it is measured. Six nanograms of mercury can be detected. Willis 93) employed more conventional methods to determine 0.04 ppm of mercury in urine by extracting it with APDC into methyl-n-amyl ketone. Berman n°) extracted mercury with APDC into MIBK to determine 0.01 ppm. 

The first fractionation of urinary ampholytes in this way was carried out by Boulanger et al. (BIO) in 1952 with the use of ion-exchange resins. They had designed this procedure previously for the fractionation of ampholytes in blood serum (B8). According to this method, deproteinized urine was subjected to a double initial procedure aiming at the separation of low-molecular weight substances from macro-molecular ones. One of the methods consisted of the fractionation of urinary constituents by means of dialysis, the second was based on the selective precipitation of urinary ampholytes with cadmium hydroxide, which, as had previously been demonstrated, permits separation of the bulk of amino acids from polypeptides precipitated under these circumstances. Three fractions, i.e., the undialyzable part of urine, the dialyzed fraction, and the so-called cadmium precipitate were analyzed subsequently. 

The urinary excretion of cadmium itself bears no known relationship to the severity or duration of exposure and is only a confirmation of absorption. Absorbed cadmium is retained by the body to a large extent, and excretion is very slow. ... 

N-(2,3-Dimercaptopropyl)phthalamidic acid (41, DMPA) has been shown to form relatively stable complexes with cadmium, zinc and mercury312. DMPA has also been shown to enhance faecal and urinary excretion of mercury in mice and arsenic in mice and rabbits. For the decorporation of arsenic, taken in as arsine, the administration of 3-(tolylthio)propane-l, 2-dithiol (42) has been proposed in the USSR313. ... 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

Gregus and Klaassen carried out a comparative study of fecal and urinary excretion and tissue distribution of eighteen metals in rats after intravenous injection. Total (fecal + urinary) excretion was relatively rapid (over 50% of the dose in 4 days) for cobalt, silver and manganese between 50 and 20% for copper, thallium, bismuth, lead, cesium, gold, zinc, mercury, selenium and chromium and below 20% for arsenic, cadmium, iron, methylmercury and tin. Feces was the predominant route of excretion for silver, manganese, copper, thallium, lead, zinc, cadmium, iron and methylmercury whereas urine was the predominant route of excretion of cobalt, cesium, gold, selenium, arsenic and tin. Most of the metals reached the highest concentration in liver and kidney. However, there was no... 

Transferrin, fhe iron-transporting protein, occurs in urine at concentrations that are about 15 times lower fhan that of albumin. The protein has a shghtly larger effective molecular radius (around 4.0 run) than albumin (3.6 run). Its detection in fhe urine allows a more sensitive indicator of early glomerular involvement in some nephropathies such as cadmium nephropathy. A strong association has been found between the presence of albumin and transferrin in fhe urine of patients with fhe nephrotic syndrome. In these patients, increased transferrin synthesis is insufficient to compensate for urinary losses and plasma levels are reduced [94]. 

Kobayashi E, Suwazono Y, Honda R, Dochi M, Nishijo M, KidoT, Nakagawa H. Serial changes in urinary cadmium concentrations and degree of renal tubular injury after soil replacement in cadmium-polluted rice paddies.Toxicol Lett. 2007 Nov 1. 

The functional changes in chronic lead nephropathy appear to be less specific than those observed in acute poisoning. As in other forms of interstitial nephritis, proteinuria and glycosuria are initially absent. In contrast to cadmium nephropathy, the excretion of a large array of urinary marker proteins such as retinal binding protein, lysozyme, and iriicroglobulin [33, 34] is not increased in the absence of a reduced GFR. 

Cadmium levels in blood are generally recognised as a biomarker of recent exposure to cadmium. It can also be used as biomarker of cumulative internal dose and accumulation of cadmium, buf only when fhere is long-term (decade long) continuous exposure, for example in subsistence farmers consuming their own crops. Cadmium levels in urine are a widely recognised biomarker of cumulative internal dose, kidney and body burden of Cd. Dose-response relationships between urinary Cd and occurrence of kidney effects are described in the subsequent sections of this chapter "Sweden", "Japan", "Belgium", and "Other countries". 

Some causal relations among various urinary indices were identified using path analysis method. Cadmium-induced renal dysfunction develops in the following order Cd exposure —> increased p2-microglobulin and/or metallothionein —> increased excretion of amino-nitrogen and/or total protein —> increased excretion of glucose [76]. 

Table 2. Proteinuria and urinary cadmium in cadmium-exposed and non-exposed subjects.

Table 5. Thresholds of urinary cadmium concentration for abnormal values of urinary markers of renal effects found in male workers with chronic occupational cadmium exposure.

Urinary markers Cut-off values Threshold effect concentration of urinary cadmium (pg Cd/g creatinine)... 

Upper limit of normal, defined as the 95 centile of the values in control workers with a urinary cadmium concentration < i pg Cd/g creatinine. 

A striking and unexpected outcome of the Cadmibel study was the clear-cut interference of fhe low-level Cd exposure with calcium metabolism. For example, when urinary Cd excretion increased twofold, serum alkaline phosphatase activity and urinary calcium excretion rose by 3-4% and 0.25 mmol/24h respectively [142]. The dose (CdU)-response rate of increased calciuria (>9.8 mmol/24h) suggested a 10% prevalence of hy-percalciuria when CdU exceeded 1.9 pg Cd/24h [38]. Hypercalciuria should be considered an early adverse tubulotoxic effect, because it may exacerbate the development of osteoporosis, especially in the elderly. A prospective study from 1992-1995 (median follow-up of 6.6 years) in the above-mentioned Cadmibel subcohort from the rural area showed for a two-fold increase in urinary Cd a significant (p<0.02) decrease of 0.01 g/ cm in forearm bone density in post-menopausal women. In addition, the relative risks associated with doubled urinary Cd were 1.73 (95% Cl 1.16-2.57 p=0.007) for fractures in women and 1.60 (0.94-2.72 p=0.08) for height loss in men. Cadmium excretion in the four... 

In some Chinese areas there are combined exposures to cadmium and inorganic arsenic. It was shown that there is a strong interaction between these two toxicants for induction of adverse renal effects in terms of tubular markers like increased p2-microglobuIin and glomerular marker urinary albumin [158]. 

Nordberg GF, Garvey JS, Chang CC. Metallothionein in plasma and urine of cadmium workers. Environ Res 1982 28 179-182. Roels HA, Eauwerys R, Buchet JP, Bernard A, Garvey JS, Linton HJ. Significance of urinary metallothionein in workers exposed to cadmium. Int Arch Occup Environ Health 1983 52 159-166. 

Tohyama C, Shaikh ZA, Nogawa K, Kobayashi E, Honda R. Elevated urinary excretion of metallothionein to environmental cadmium.Toxicology 1981 20 289-297. 

Piscator M. Proteinuria in chronic cadmium poisoning. I. An electrophoretic and chemical study of urinary and serum proteins from workers with chronic cadmium poisoning. Arch Environ Health 1962 4 607-621. 

Kjellstrom T, Evrin P-E, Rahnster B. Dose-response analysis of cadmium induced tubular proteinuria. A study of urinary Pj-mi-croglobulin excretion among workers in a battery factory. Environ Res 1977 13 303-317. 

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