Studies of mortality rates from nonmalignant renal disease in occupational cohorts exposed to uranium appear in Table 4.14. In the seven cohort studies of occupational exposure and mortality from renal disease, only one study shows an excess mortality from renal disease. In that study (Waxweiler et al., 1983), all of the cases were in short-term workers, and four of the six deaths occurred within 8 years of initial employment at the uranium mill, which implies that the apparent excess mortality is not related to the extent of exposure to uranium. In most of these studies, the authors measured death rates from all genitourinary causes instead of focusing on diseases of the kidney, the part of the genitourinary tract in which uranium accumulates. The largest study (Frome et al., 1990) had 52 deaths from chronic nephritis, compared with 52.65 expected deaths (SMR = 99).
The potential effect of uranium exposure on kidney function in humans has been examined in studies with varying doses and with different routes of exposure. This information includes case reports and studies with small numbers of subjects.
Intravenous injections. Hodge and colleagues (1973) described six patients with normal kidney function who were injected with uranyl nitrate (6.3–109 μg/kg over a 1- to 2-day period). Transient proteinuria and catalasuria occurred 4–6 days after the injection in the two patients who received the highest dose (>42 μg/kg). The authors used these observations to estimate the uranium dosage that is associated with minimal tubular kidney damage.
Bernard (1958) administered 4–50 mg of uranium compounds intravenously to eight terminally ill patients with brain tumors. Transient proteinuria and catalasuria occurred in patients receiving uranium doses >70.9 μg/kg. There was no evidence at autopsy of acute damage to the renal tubules. Based on these observations, the author estimated that the minimal uranium dose that will produce catalasuria and albuminuria is about 0.1 mg/kg.
Oral exposure. There are a few case studies with limited information about the effects of orally administered uranium compounds. Oral ingestion of uranyl nitrate at dosages as high as 925 mg, three times per day, did not cause abnormalities on routine urinalysis (Morrow et al., 1980). A volunteer who orally ingested 1 g of uranyl nitrate (0.47 g uranium) experienced vomiting, diarrhea, and slight albuminuria (Stopps and Todd, 1982). In the only other reported oral ingestion of uranium salts with follow-up measurements, 10.8 mg of uranyl nitrate had no effects on kidney function in four patients (Stopps and Todd, 1982).