The section following immediately discusses nephrotoxicity. Discussions of genitourinary cancer follow later in the chapter.

Hereditary Susceptibility to Nephrotoxicity

Hereditary renal conditions are a documented but infrequent cause of end-stage renal disease (ESRD). The most prevalent hereditary renal disease is cystic kidney disease, which accounts for 3.4% of the cases of ESRD. Other hereditary or congenital renal disease accounts for 0.9% of the cases of ESRD (NIH, 1993). An intriguing observation regarding the relationship between hereditary factors and ESRD comes from a case-control study of 325 men in which occupational exposure was sought as an etiologic explanation of their ESRD. Only patients whose diagnoses were compatible with toxicant-induced renal injury were included in the analysis; patients with other known causes of renal failure were excluded. That ESRD was most strongly associated with a family history of renal disease (odds ratio, 9.30:1) (Steenland et al., 1990), not with occupational exposure, suggested the presence of hereditary susceptibility.

Substantial evidence supports a sex-related predilection for susceptibility to various nephrotoxicants. For example, male rats are more sensitive than female rats to the nephrotoxic effects of carbon tetrachloride and aminoglycoside antibiotics (Bennett et al., 1991). In contrast, Moore et al. (1984) demonstrated a higher susceptibility of women than of men to the nephrotoxic effects of aminoglycoside antibiotics. In any case, there seems to be a sex-related effect in both rats and humans; whether these differences are genetic in origin remains to be determined.

Direct evidence of race as a risk factor in toxicant-induced renal injury is lacking, but blacks and some other minority groups are highly susceptible to other forms of renal disease, such as has been demonstrated for the renal disease due to hypertension and diabetes mellitus (see Chapter 2) (NIH, 1992).

Inherited renal disorders might influence susceptibility to toxic injury. The potential impact of genetic factors on the renal response to environmental agents has not been widely appreciated or reviewed. One important and complicating aspect is the highly variable penetrance or expression of most of the genetic abnormalities that involve the kidney. Many people who carry genes for renal abnormalities might be only mildly affected or remain completely asymptomatic for many decades. Although it might be relatively easy to identify the first person in a genetic line with overt clinical manifestations of genetic kidney disease, a much larger pool of asymptomatic people might also be at higher risk than normal for damage from exposure to biohazards.

A number of inherited disorders affect renal development or structure; these disorders have been extensively documented, and their clinical features

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