Lead in kidney

Barregard, L., Svalander, C., Schiitz, A., Westberg, G., Blohme, I., Molne, J., Attman, P.-O., and Haglind, P., Cadmium, mercury and lead in kidney cortex of the general Swedish population A study of biopsies from living kidney donors, Environment and Health Perspectives, 107, 867-871, 1999. 

The significance of trace amounts of organolead residues in birds is unknown. Trialky Head seems to concentrate in avian kidney, but contributes less than 5% of the total amount of lead in kidneys (Johnson et al. 1982). 

Carroll, K.G., SpineUi, E.R., Goyer, R.A., 1970. Electron probe microanalyzer localization of lead in kidney tissue of poisoned rats. Nature 227, 1056. 

The absorption, distribution, and accumulation of lead in the human body may be represented by a three-part model (6). The first part consists of red blood cells, which move the lead to the other two parts, soft tissue and bone. The blood cells and soft tissue, represented by the liver and kidney, constitute the mobile part of the lead body burden, which can fluctuate depending on the length of exposure to the pollutant. Lead accumulation over a long period of time occurs in the bones, which store up to 95% of the total body burden. However, the lead in soft tissue represents a potentially greater toxicological hazard and is the more important component of the lead body burden. Lead measured in the urine has been found to be a good index of the amount of mobile lead in the body. The majority of lead is eliminated from the body in the urine and feces, with smaller amounts removed by sweat, hair, and nails. 

C1C-3, -4 and -5 form the second branch of the CLC gene family. These proteins are 80% identical, and with the exception of C1C-5, which is most highly expressed in kidney and intestine, show a broad expression pattern. C1C-3 to C1C-5 reside in intracellular membranes of the endocytotic pathway [4]. Disruption of C1C-5 leads to a defect in endocytosis in mouse... 

Excessive lead exposure has been implicated as a causative agent in kidney disease associated with gout (Batuman et al. 1981). A correlation was found between the amount of mobilizable lead and the degree of renal impairment in 44 veterans with gout. The 44 gout patients were similar with respect to age,... 

No increase in kidney weight was noted in mice continuously exposed to 1.6 mg lead/m3 as lead nitrate for 28 days (Hillam and Ozkan 1986). No other studies were located regarding renal effects in animals after inhalation exposure to inorganic lead. These results are presented in Table 2-2 and plotted in Figure 2-1. 

Information is available on the renal toxicity of ingested lead in several species, including rats, dogs, monkeys, and rabbits. The results indicate that histopathological changes in the kidneys of lead-treated animals are similar to those in humans (see Section 2.2.1.2). Reduced glomerular filtration rates and aminoaciduria were reported in some of the animal studies. Key animal studies on lead-induced renal toxicity will be discussed below. 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

Limited information was located regarding dermal absorption of inorganic lead in animals. An early study reported that lead acetate was absorbed from the clipped skin of rats, as determined by an increase in the concentration of lead in the kidneys relative to controls (Laug and Kunze 1948). It was further shown in that study that mechanical injury to the skin significantly increased the penetration of lead and that the penetration of lead from lead arsenate was significantly less than from lead acetate. 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

Kidney function has been evaluated not only in relation to PbB levels, but also in relation to bone lead concentrations, which provide a better assessment of cumulative dose of lead to the kidneys than blood lead. In a study of lead-exposed workers whose mean tibia lead was three times that of controls (66... 

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