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were also measured. Linear and weighted robust regression methods were used to account for highly influential observations. Separate analyses were conducted for men and women and accounted for age, smoking status, and estrogen use.

Through robust and linear-regression analyses, uranium exposure was shown to be associated with increased CTx in men (uranium in water, p = 0.05 and 0.01; daily intake, p = 0.16 and 0.02; and cumulative intake, p = 0.16 and 0.03, respectively). Uranium concentrations in drinking water appeared to be associated with increased osteocalcin (p = 0.19; p = 0.04 in linear-regression analysis). Uranium exposure was not related to any biomarkers of bone metabolism in women. P1NP was not associated with uranium exposure.

Kurttio et al., 2006a

In 2003, Kurttio and colleagues continued their assessment of nephrotoxic effects of naturally occurring uranium in well water, focusing on measures associated with renal-cell toxicity and renal tissue damage. The study population was based on a previous study group in which 325 participants were selected in the evaluation of basic renal function (Kurttio et al., 2002). A third questionnaire was sent to the previous study participants; 222 responded, of whom 202 provided samples for a number of tubular and glomerular markers. Details on residential history, daily well-water consumption and use, medical history, use of medication, and smoking history were collected, and only current well-water users were selected. The authors excluded one person who had recently taken methotrexate. The final study population consisted of 95 men and 98 women in 124 households in which drilled wells were the primary source of drinking water for an average of 16 years (range, 5-40 years). The mean age was 56 ± SD 12 years. Some 6% were smokers, and 56% reported never having smoked. The average BMI was 26 ± 4 kg/m2. Thirty-nine study participants (20%) reported regular use of analgesics 1 year before study enrollment.

Urine, blood, nail, hair, and household water (kitchen-tap) samples were collected from study participants in households that had consumed well water for at least 1 week continuously. Blood pressure, body weight, and height were also measured. As in the previous study, urinary uranium was measured, as were daily intake, daily intake per unit body weight, intake from drinking water, and cumulative intake. A number of biomarkers were measured in urine and serum samples selected as indicators of cell toxicity and renal dysfunction. Cytotoxic measures included N-acetyl-γ-D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase, and γ-glutamyltransferase. Concentrations of α-glutathione-S-transferase, calcium, phosphate, and glucose served as indicators of proximal tubular and glomerular dysfunction. As in the previous study, the authors calculated values for calcium and phosphate fractional excretion, in addition to glucose excretion and creatinine clearance. Linear regression was used to model outcome

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