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.

Abstract-The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at Ϫ174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intimamedia thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (Pϭ0.015) associated with IMT, and this relation remained (Pϭ0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (Pϭ0.036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (PϽ0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis. Key Words: stromelysin-1 Ⅲ interleukin-6 Ⅲ DNA polymorphism Ⅲ B-mode ultrasonography Ⅲ carotid atherosclerosis Ⅲ population sample

Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.