Cadmium excretion

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... 

The total body burden of cadmium is less than 1 pg at birth, which gradually increases with age, up to 50 years. At this age, one who has essentially been unexposed to cadmium may accumulate 20-30 mg of cadmium in the body (Medeiros et al., 1997). The biological half-time has been estimated to be 15-30 years in human beings (Piscator, 1982). The placenta acts only as a partial barrier against the fetal exposure. Before the formation of the placenta, cadmium reaches the embryo. Later, cadmium is deposited in the placenta, and there is limited passage of cadmium into the fetus. Moreover, there is only minimal cadmium excretion in breast milk (Gerhardsson and Skerfving, 1996). 

Cadmium in urine reflects the body burden of cadmium, especially the cadmium concentration in the main accumulation organ, the kidney (organ-specific accumulation). Therefore, it can be regarded as indicator of the cumulative long term exposure. As long as the renal function remains normal, the concentration of cadmium in urine is well correlated with the total cadmium body burden. After cadmium-induced irreversible tubular renal dysfunction with microproteinuria, the cadmium excretion in urine tends to increase, as cadmium is released from renal depots [2,3]. 

The reversibility of glomerular lesions induced by cadmium is still under discussion [61,76]. Tubular proteinuria (p2-M and RBP in urine) between 300 and 1000 pg/g creatinine might be reversible [61], but more severe tubular proteinuria (i.e., more than 1000 pg p2-M/g creatinine) seems to be irreversible [61,77]. A large study with 1699 subjects (aged 20-80 years) of the general population showed a 10% probability of values of urinary excretion of RBP, NAG, p2-M, amino acids, and calcium being abnormal when cadmium excretion exceeded 2 pg/24 h [78]. 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Biological half times of cadmium in humans is lengthy. Based on body burden and excretion data, cadmium may remain in the human body for 13 to 47 years. Although cadmium is excreted primarily in urine and feces, it tends to increase in concentration with the age of the organism and eventually acts as a cumulative poison (Hammons et al. 1978). These phenomena have not been documented adequately in wildlife species. 

Cadmium occurs naturally as sulfide co-deposited with zinc, copper, and lead sulfides. It is produced as a by-product in above-mentioned metal processing. Similar to lead and mercury, this heavy metal has no known biological functions in living organisms, and accordingly its accumulation in food and water leads to undesirable consequences to biota. Cadmium toxicology is related to dangerous influence to CNS and excretion systems, firstly, on kidney. 

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. ... 

Cadmium is bound to proteins and red blood cells in blood and transported in this form, but 50% to 75% of the body burden is located in the liver and kidneys. The half-life of cadmium in the body is between 7 and 30 years, and it is excreted through the kidneys, particularly after they become damaged. 

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

Cadmium is a cumulative toxicant with a biologic half-life of up to 30 years in humans. More than 70% of the cadmium in the blood is bound to red blood cells accumulation occurs mainly in the kidney and the liver, where cadmium is bound to metallothionein. In humans the critical target organ after long-term exposure to cadmium is the kidney, with the first detectable symptom of kidney toxicity being an increased excretion of specific proteins. 

Chronic effects are of particular concern because cadmium is very slowly excreted from the body, with a half-life of about 30 years. Thus low levels of exposure can result in considerable accumulation of cadmium. The main organ of damage following long-term exposure is the kidney, with the proximal tubules being the primary site of... 

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. ... 

The results of studies on animals show that cadmium is an extremely toxic metal. Cadmium is poorly excreted by the human body and although only 5-10% of that ingested is absorbed, it does accumulate in the body over time with renal damage being caused by long-term exposure.14 One sign of this damage is proteinuria (the appearance of increased levels of unaltered proteins in the... 

The metallothionines, for example, take care of transport and excretion of metal ions such as cadmium, and excesses of zinc and copper. A complete crystal structure of a metallothionine has been published. The protein structure contains seven metal ions coordinated by 20 cysteine residues in two regions of the protein. 

Liu JX, Nordberg GF. 1995. Nephrotoxicities of aluminum and/or cadmium-metallothionein in rats Creatinine excretion and metabolism of selected essential metals. Pharmacol Toxicol 77 155-160. 

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