Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.

Uranium accumulates in bone, affects bone metabolism in laboratory animals, and when ingested in drinking water increases urinary excretion of calcium and phosphate, important components in the bone structure. However, little is known about bone effects of ingested natural uranium in humans. We studied 146 men and 142 women 26–83 years of age who for an average of 13 years had used drinking water originating from wells drilled in bedrock, in areas with naturally high uranium content. Biochemical indicators of bone formation were serum osteocalcin and amino-terminal propeptide of type I procollagen, and a marker for bone resorption was serum type I collagen carboxy-terminal telopeptide (CTx). The primary measure of uranium exposure was uranium concentration in drinking water, with additional information on uranium intake and uranium concentration in urine. The data were analyzed separately for men and women with robust regression (which suppresses contributions of potential influential observations) models with adjustment for age, smoking, and estrogen use. The median uranium concentration in drinking water was 27 μg/L (interquartile range, 6–116 μg/L). The median of daily uranium intake was 36 μg (7–207 μg) and of cumulative intake 0.12 g (0.02–0.66 g). There was some suggestion that elevation of CTx (p = 0.05) as well as osteocalcin (p = 0.19) could be associated with increased uranium exposure (uranium in water and intakes) in men, but no similar relationship was found in women. Accordingly, bone may be a target of chemical toxicity of uranium in humans, and more detailed evaluation of bone effects of natural uranium is warranted.

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