PRINCIPLES OF TOXICOLOGY - Biology East Borneo

6.3 ADVERSE EFFECTS OF CHEMICALS ON THE KIDNEY 139TABLE 6.2 Industrial Operation with Exposure to Nephrotoxicants aIndustrial operationAmalgam manufacturersChemistsChloralkaliDry cleaningManufacturing batteriesManufacturing cellulose acetateMetal degreasingPaint manufacturersPlumbersNephrotoxicantMercuryChloroformMercuryPerchloroethyleneMercury, Lead, CadmiumDioxanePerchloroethyleneLead, CadmiumLeada List in alphabetical order.consistent proteinuria, and cadmium-induced kidney damage may appear years after workers areremoved from exposure.In Japan excessive cadmium intake was also linked to a peculiar form of renal osteodystrophyknown as “ouch-ouch disease” or “itai-itai byo.” It has been proposed that this disease is caused byexcessive loss of cadmium and phosphorus in the urine, combined with dietary calcium deficiency.The kidney naturally accumulates cadmium. Normally cadmium accumulates in the kidney overthe lifetime of the individual until the age of 50. About 50 percent of the total burden of cadmium inthe body is borne by the liver and kidney, with the kidney having 10 times the concentration of theliver. Cadmium induces synthesis in the liver of metallothionein, a protein with a high binding affinityfor cadmium. While metallothionein acts to protect certain organs, such as the testes, from cadmiumtoxicity, it may play a role in cadmium toxicity in the kidney. After the available metallothionein inproximal tubule cells is overcome by high cadmium concentrations, the free cadmium exerts toxiceffects on the cells in the proximal tubule.Chronic cadmium exposure has also been implicated as a factor in hypertension. However, whilethe development of hypertension may involve the kidney, the role of cadmium in the etiology ofhypertension in humans is far from conclusive.Mercury Inorganic mercury (Hg 2+ ) is a classical nephrotoxicant. It is used as a model compoundfor producing kidney failure in animals, and massive doses of mercuric ion can damage the proximaltubule and cause acute renal failure. A brief polyuria is followed by oliguria or even anuria. The anuria(kidney failure) leads, of course, to a life-threatening accumulation of bodily wastes and may last manydays. If recovery occurs, a polyuria follows, which is probably caused by a decreased sodiumabsorption in the proximal tubule. Such disturbances in tubular function may last several months.Acute exposure to high concentrations of mercury is rare; usually mercury exposure occurs at lowerdose rates. The part of the nephron most sensitive to mercuric ion toxicity is the pars recta or straightportion of the proximal tubule (Figure 6.3). Early damage is characterized by the presence of enzymesin the urine that are normally found in the brush border portion of the cells lining the tubule. Furtherdamage results in the presence of intracellular enzymes from these cells in the urine. Longer-termexposure and damage can lead to the presence of glucose, amino acids, and proteins in the urine. Alsoassociated with long-term exposure to mercury is a reduction in the GFR caused by vasoconstriction,tubular damage, and damage to the glomerulus.Chloralkali workers exposed to mercury have increased glomerular dysfunction and elevatedexcretion of high-molecular-weight proteins. 2-Microglobulin has been found at elevated levels in theblood plasma of these workers, but levels in urine were not increased.Lead Lead is a known nephrotoxicant in humans. Lead causes damage principally to the proximaltubule of the nephron. Reabsorption of glucose, phosphate, and amino acids is depressed in the