The Nephrotoxicity of Lead in Human Populations

This chapter describes the acute and chronic nephrotoxic effects of lead in human populations. These effects have long been recognized in chronic adult occupational lead exposures and in nonoccupational adult exposures arising from dietary Pb intakes, producing disorders such as gouty nephropathy. In acute childhood Pb exposure, severe kidney effects in the form of Fanconi syndrome were identified in the early pediatric literature. The syndrome often co-occurred with acute encephalopathy. 

Numerous reports on Pb-associated kidney injury in various subsets of human populations have been published over the years, and Pb nephropathy has been covered in various expert consensus reports for public agency or scientific organizations, such as those of the U.S. EPA (1977, 1986, 2006), the U.S. ATSDR (2007), the WHO (1995), and the NAS/NRC (1972, 1980, 1993). Individual monographs and critical reviews on the topic have also appeared (Ekong et al., 2006 Loghman-Adham, 1997 Wedeen, 1984, 1982). 

More recent evidence in the occupational and environmental health literature identifies two general forms of nephropathological and nephrotoxicolo-gical responses to lead in lead workers and others. Acute nephrotoxic effects of lead present clinically and functionally with a different array of signs and symptoms than the chronic lead nephropathy syndrome, as discussed below. 

Trace Metals and other Contaminants in the Environment, Vfdume 10 

Lead nephropathy as a toxicological topic has presented various interpretive clinical and empirical dilemmas. Some appear to have resolved to some extent. Some are mainly confined to nephropathic responses per se. Some are shared with other lead-associated toxic endpoints. A classical endpoint in Pb-induced nephropathy is a reduced estimated or measured glomerular filtration rate (GFR), typically employing creatinine clearance rates, in tandem with measurements of blood urea nitrogen (BUN) and serum creatinine levels. Such declines in GFR are proportional to the level of PbB in chronic injury, subsequent to any transitory hyperfiltration. 

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Cardiovascular effects of Pb in humans are the subject of Chapter 13, particularly with respect to effect potency in older exposure subjects but with inclusion of other risk groups. Cardiovascular effects, while inconsistently quantified across human populations, have been identified in multiple epidemiological studies, supported by a number of experimental data sets appearing in the global literature. Chapter 14 on human reproductive and developmental impacts of lead exposures presents the more useful data across several risk groups within human populations. Chapter 15 discusses adverse effects of lead on the renal system as nephrotoxicity is considered to occur across both occupational and nonoccupational subsets of human populations and subsets within nonoccupational categories. Discussions in Chapter 15, much like those in Chapter 18 on immunotoxicity, have benefited from quite recent findings. 

This chapter discusses the hematological effects of lead in both human populations and various experimental animal test systems. Lead hematotoxicity, in common with effects such as neurotoxicity, nephrotoxicity, and cardiovascular impairments, has long been recognized as accompanying chronic childhood and adult lead exposures within various Pb exposure settings. 

Lead exposures in diverse human populations produce both acute and chronic nephrotoxic effects. The chronic kidney disease association with occupational Pb exposures in the clinical literature, dating to the nineteenth century, was typically characterized as a glomerulonephritic disease histo-pathologically. This traced to the absence of evaluation of the temporal course of Pb-induced nephropathy, particularly the acute effects. 

Consequently, this review is designed to briefly summarize many of the available techniques for accurate measurements of environmental and human lead contamination. This includes the importance of ultraclean techniques for lead analysis as well as brief descriptions of some current and emerging analytical techniques for measuring lead exposures in humans. The descriptions are preceded by abbreviated discussions of the chemical properties of lead, natural and anthropogenic variations in its stable isotopic composition, and historical records of lead contamination in the environment. The report concludes with a summary of some indirect methods of measuring lead exposure and toxicity in humans. Much of the material in this report is based on reviews written for several recent reports Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations (NRC 1993), Lead in the Biosphere Recent Trends (Smith and Flegal 1995), and In Vivo Measurement and Speciation of Nephrotoxic Metals (Smith and McNeill 1995). 

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