Kidney, cadmium toxicity

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. 

Pels LM, Bundschuh I, Gwinner W, et al. Early urinary markers of target nephron segments as studied in cadmium toxicity. Kidney Int Suppl 1994 47 S81-8. 

Gobe G, Crane D (2010) Mitochondria, reactive oxygen species and cadmium toxicity in the kidney. Toxicol Lett 198(1 ) 49-55. doi 10.1016/j.toxlet.2010.04.013... 

Jamall IS, Naik M, Sprowls JJ, et al. 1989. A comparison of the effects of dietary cadmium on heart and kidney antioxidant enzymes Evidence for the greater vulnerability of the heart to cadmium toxicity. J Appl Toxicol 9(5) 339-345. 

Jin T, Nordberg GF. Cadmium toxicity in kidney cells. Resistance induced by short term pretreatment in vitro and in vivo. Acta Pharmacol Toxicol 1986 58 137-143. 

Cadmium occurs only in one valency state (2 ) and does not form stable alkyl compounds or other organometallic compounds of known toxicological significance. Cadmium initially is distributed to the liver and then redistributes slowly to the kidney as cadmium-metallothionein (Cd-MT), with 50% of the total-body burden in the liver and kidney after distribution. Cadmium and several other metals induce the expression of metallothionein, a cysteine-rich protein with high affinity for metals such as cadmium and zinc. Metallothionein protects cells against cadmium toxicity by preventing the interaction of cadmium with other proteins. 

The gravity of cadmium-induced renal damage is compounded by the fact there is no medical treatment to prevent or reduce the accumulation of cadmium in the kidney (Ex. 8-619). Dr. Friberg, a leading world expert on cadmium toxicity, indicated in 1992, that there is no form of chelating agent that could be used without substantial risk. He stated that tubular proteinuria has to be treated in the same way as other kidney disorders (Ex. 29). 

The continuai accumulation of cadmium is the basis for its chronic noncarcinogenic toxicity. This accumulation makes the kidney the target organ in which cadmium toxicity usually is first observed (Piscator 1964). Renal damage may occur when cadmium levels in the kidney cortex approach 200 pg/g wet tissue-weight (Travis and Haddock 1980). 

In animal studies, decreased zinc status also contributes to lead and cadmium toxicity. In studies with rats, Cerklewski and Forbes (1976) demonstrated that an increase of zinc in the diet decreased the tissue lead levels and reduced other indicators of lead toxicity. Cerklewski (1979) also demonstrated that high levels of zinc fed to pregnant rats resulted in significantly lower levels of lead in the blood and liver of the rat pups. Using Japanese quail, Jacobs et al. (1977) reported that supplemental zinc markedly decreased concentrations of cadmium in the liver, kidney and small intestine, while Fox et al. (1979) showed that marginally adequate levels of dietary zinc markedly increased retention of cadmium in the duodenum, jejunum, ileum and liver as compared with zinc-supplemented birds. The association between increased lead burdens and lower serum zinc levels in children was reported by Markowitz and Rosen (1981). However, the mean levels of serum zinc in the children with elevated blood lead levels were not considered to be outside the lower limits of normal for plasma cited by Hambidge (1977). 

Heavy metals, sueh as cadmium, lead and mercury, have been used in certain dyes and pigments, which are used for textiles. These metals can accumulate in the body over time and are highly toxic, with irreversible effects including damage to the nervous system (lead and mercury) or the kidneys (cadmium). Cadmimn is also known to cause cancer. 

Probably the most notorious case of cadmium toxicity was the disorder known as Itai-Itai disease which occurred in Japan after World War II. This was essentially an osteomalacia associated with serious kidney damage and is discussed in Chapter 6.6.4. Changes in bones associated with cadmium toxicity have been described by Nicaud [44] and a specific effect is proteinuria caused by damage to kidney tubules [45-47]. Acute necrosis of the testes has also been reported [48] at relatively low doses of cadmium, although this effect does not seem to be a feature of chronic cadmium toxicity. Chronic bronchitis, hypertension and cardiovascular disease have also been reported as being associated with cadmium toxicity [49]. 

The striking effects of cadmium toxicity in Japan arising from increased uptake of cadmium in locally-consumed rice grown in paddy fields irrigated with cadmium-contaminated river water have already been mentioned. The disorder involved was essentially an osteomalacia, associated with kidney damage and proteinuria, affecting villagers who were dependent on the rice crop as a main source of food. 

While severe cadmium toxicity like that which occurred near Toyama has not been found elsewhere, it is suspected that mild to moderate types of chronic cadmium toxicity may cause disorders of the kidneys leading to high blood pressure. However, the milder forms of cadmium poisoning may be counteracted by such essential minerals as calcium, copper, iron, manganese, selenium, and zinc. Therefore, a few scientists believe that high ratios of cadmium to zinc in the diet and in the various tissues of the body are better indicators of potential cadmium toxicities than the dietary and tissue levels of this toxicant alone. 

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