Cadmium proteinuria

The applicability of quantitative and qualitative methods of protein determination for the demonstration of cadmium proteinuria, Arch. Environ. Health, 1962,5, 325-332. 

Lauwerys RR, Bernard A, Roels HA, Buchet J-P, Viau C (1984) Characterization of cadmium proteinuria in man and rat. Environ Health Perspect, 54 147-152. 

Potts, C.L. (1965). Cadmium Proteinuria—The Health Battery Workers Exposed to Cadmium Oxide dust. Ann Occup Hyg, 3 55-61, 1965. 

Roels HA, Lauwerys R, Materne D, Buchet JP (1975) Study on cadmium proteinuria glomerular dysfunction, an early sign of renal impairment In Proceedings of the International Symposium on Recent Advances in the Assessment of the Health Effects of Environmental Pollution (Paris, 1974) Commission of the European Communities, Luxembourg, Vol. 2, pp. 631-641... 

Potts, C.L. (1965) Cadmium proteinuria—the health of hatteiy workers exposed to cadmium oxide dust. Ann. Occup. Hyg. 8, 55-62. 

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. 

Tsuchiya K Proteinuria of workers exposed to cadmium fume. Arch Environ Health 14 875-890, 1967... 

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... 

Cadmium in the body is known to affect several enzymes. It is believed that the renal damage that results in proteinuria is the result of cadmium adversely affecting enzymes responsible for reabsorption of proteins in kidney tubules. Cadmium also reduces the activity of delta-aminolevulinic acid synthetase (Figure 10.3), arylsulfatase, alcohol dehydrogenase, and lipoamide dehydrogenase, whereas it enhances the activity of delta-aminolevulinic acid dehydratase, pyruvate dehydrogenase, and pyruvate decarboxylase. 

Cadmium may accumulate in the body, primarily in kidneys and liver, and has a half-life of several decades. The toxic effect occurs in the kidneys and may lead to proteinuria. A PTWI value has been established at 7 p,g kg-1 body weight equivalent to 72 p,g person-1 day-1 [9]. Cadmium has been classified as a... 

Cadmium (Cd) is a non-essensial metal used in industry as an anti-corrosive agent, and is found as a contaminant in food and also in cigarette smoke. The most serious consequence of chronic Cd poisoning is lung- and prostate cancer but the first effect during chronic intake is kidney damage, manifested by marked proteinuria [164]. Under chronic exposure, cadmium is primarily taken up by the liver, where it induces synthesis of metallothionein (MT) and induces formation of cadmium-metallothionein complexes. 

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. 

The first observations on adverse renal effects of cadmium (Cd) exposure in humans were made by Friberg in the late 1940s [1]. He reported a high prevalence of proteinuria (65% using the nitric acid test and 81% using the trichloroacetic acid test) in Cd-exposed workers. 

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

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. 

Friberg L. Proteinuria and kidney injury among workmen exposed to cadmium and nickel dust. J Ind Hyg Toxicol 1948 30 32-36. 

PIscator M. Proteinuria In chronic cadmium poisoning. III. Electrophoretic and Immuno-electrophoretic studies on urinary proteins from cadmium workers, with special reference to the excretion of low molecular weight proteins. Arch Environ Health 1966 12 335-344. 

Cardenas A, Bernard AM, Lauwerys R. Disturbance of sialic acid metabolism by chronic cadmium exposure and Its relation to proteinuria.Toxicol AppI Pharmacol 1991 108 547-558. 

The association between metal exposure and renal failure can be approached from two points of view. On the one hand environmental/industrial exposure to heavy metals, more particularly, lead, cadmium and mercury and other inorganic substances such as silicon has been linked to a reduced renal function and/or the development of acute or chronic renal failure [1]. This issue has been dealt with in other chapters of this book. On the other hand patients with chronic renal failure, especially those treated by dialysis are at an increased risk for trace element disturbances (Figure 1). Indeed in these subjects the reduced renal function, the presence of proteinuria, metabolic alterations associated with renal insufficiency, the dialysis treatment, medication etc. all may contribute to either accumulation or deficiency of trace metals. With regard to aluminum intensive research on the element s toxic effects has been performed in the past. Recently, new metal-containing medications have been introduced of which the potential toxic effects should be considered and put in a justified context. 

Trace metal disturbances may be due to the uremia per se. Indeed, as the urinary excretion route is an important pathway of elimination of many trace elements, i.e. silicon, strontium, aluminum,... impairment of the kidney will be an important determinant of their accumulation, whilst in the presence of a reabsorptive defect a number of trace elements, especially those that are reabsorbed because of their essential role, be lost resulting in a deficient state. The presence of proteinuria may reasonably result in losses of protein bound elements. It has also been shown also that residual renal funchon may importantly alter the accumulation and hence toxic effects of aluminum [2]. In uremia translocation of a particular metal from one tissue to another may also occur. As an example, under normal circumstances the kidney is an important target organ for cadmium. In chronic renal failure however, possibly as a consequence of a reduction in binding proteins (e.g. metallothionein), the concentrahon of cadmium in this tissue decreases to extremely low levels which... 

Since the kidneys are the main depot for cadmium, they are of greatest concern for cadmium toxicity. Cadmium interferes with the proximal tubule s reabsorption function. This leads to abnormal actions of uric acid, calcium, and phosphorus. Amino aciduria (amino acids in the urine) and glucosuria (glucose in the urine) result in later stages, proteinuria (protein in the urine) results. When this happens, it is assumed that there is a marked decrease in glomerular filtration. Long-term exposure to cadmium leads to anemia, which may result from cadmium interfering with iron absorption. 

Another example is cadmium, a highly toxic heavy metal. Once absorbed, cadmium in the body is mainly bound to the protein metallothionein. This protein is involved in the transport and selective storage of cadmium. A rather selective accumulation of cadmium occurs in the kidneys, leading to eventual tubular dysfunction with proteinuria (Friberg et al. 1974). 

Bernard A, Roels H, Hubermont G, Buchet JP, Masson PL, Lauwerys R (1976) Characterization of the proteinuria in cadmium-exposed workers. Int Arch Occup Environ Health, 38 19-30. 

D-penicillamine is so named because it was first isolated as an amine, from the degradation products of penicillin by Abraham et al [87]. Later studies showed the characteristic chemical behavior of D-penicillamine which involve three types of reactions, formation of disulphide links, formation of thiazolidine rings, and formation of metal complexes and chelates [67]. It was first used in 1956 in the treatment of Wilson s disease [88]. D-penicillamine has since been used in the treatment of many diseases, such as cystinuria [89], rheumatoid arthritis [90-92], systemic sclerosis [93], primary bdiary cirrhosis [94], heavy metal poisoning due to lead [95], cadmium [%], and mercury [97], and hyperviscosity syndrome [99]. In rheumatoid arthritis, D-peni-cdlamine has been widely accepted as an effective second line treatment. Despite of its effectiveness, it causes many adverse effects, such as skin rashes [99,100], taste abnormalities [100,101], hepatic dysfunction [102-104], gastrointestinal toxiciiy [99,105], proteinuria [100,106], hematuria [107, 108], thrombocytopenia [92, 109], aplastic anemia [110], lupus-like syndrome [111, 112], Goodpasture s-tike pulmonary renal syndrome [113-115], vasculitis [116,117], myasthenia gravis [118-122], polymyositis [123, 124], and dermatomyositis [125]. 

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