TY - JOUR
T1 - Associations among lead dose biomarkers, uric acid, and renal function in Korean lead workers
AU - Weaver, Virginia M.
AU - Jaar, Bernard G.
AU - Schwartz, Brian S.
AU - Todd, Andrew C.
AU - Ahn, Kyu Dong
AU - Lee, Sung Soo
AU - Wen, Jiayu
AU - Parsons, Patrick J.
AU - Lee, Byung Kook
PY - 2005/1
Y1 - 2005/1
N2 - Recent research suggests that both uric acid and lead may be nephrotoxic at lower levels than previously recognized. We analyzed data from 803 current and former lead workers to determine whether lead biomarkers were associated with uric acid and whether previously reported associations between lead dose and renal outcomes were altered after adjustment for uric acid. Outcomes included uric acid, blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-β-D-glucosaminidase (NAG) and retinol-binding protein. Mean (± SD) uric acid, tibia lead, and blood lead levels were 4.8 ± 1.2 mg/dL, 37.2 ± 40.4 μg/g bone mineral, and 32.0 ± 15.0 μg/dL, respectively. None of the lead measures (tibia, blood, and dimercaptosuccinic-acid-chelatable lead) was associated with uric acid, after adjustment for age, sex, body mass index, and alcohol use. However, when we examined effect modification by age on these relations, both blood and tibia lead were significantly associated (β = 0.0111, p < 0.01 and β = 0.0036, p = 0.04, respectively) in participants in the oldest age tertile. These associations decreased after adjustment for blood pressure and renal function, although blood lead remained significantly associated with uric acid (β = 0.0156, p = 0.01) when the population was restricted to the oldest tertile of workers with serum creatinine greater than the median (0.86 mg/dL). Next, in models of renal function in all workers, uric acid was significantly (p < 0.05) associated with all renal outcomes except NAG. Finally, in the oldest tertile of workers, associations between lead dose and NAG were unchanged, but fewer associations between the lead biomarkers and the clinical renal outcomes remained significant (p ≤ 0.05) after adjustment for uric acid. In conclusion, our data suggest that older workers comprise a susceptible population for increased uric acid due to lead. Uric acid may be one, but not the only, mechanism for lead-related nephrotoxicity.
AB - Recent research suggests that both uric acid and lead may be nephrotoxic at lower levels than previously recognized. We analyzed data from 803 current and former lead workers to determine whether lead biomarkers were associated with uric acid and whether previously reported associations between lead dose and renal outcomes were altered after adjustment for uric acid. Outcomes included uric acid, blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-β-D-glucosaminidase (NAG) and retinol-binding protein. Mean (± SD) uric acid, tibia lead, and blood lead levels were 4.8 ± 1.2 mg/dL, 37.2 ± 40.4 μg/g bone mineral, and 32.0 ± 15.0 μg/dL, respectively. None of the lead measures (tibia, blood, and dimercaptosuccinic-acid-chelatable lead) was associated with uric acid, after adjustment for age, sex, body mass index, and alcohol use. However, when we examined effect modification by age on these relations, both blood and tibia lead were significantly associated (β = 0.0111, p < 0.01 and β = 0.0036, p = 0.04, respectively) in participants in the oldest age tertile. These associations decreased after adjustment for blood pressure and renal function, although blood lead remained significantly associated with uric acid (β = 0.0156, p = 0.01) when the population was restricted to the oldest tertile of workers with serum creatinine greater than the median (0.86 mg/dL). Next, in models of renal function in all workers, uric acid was significantly (p < 0.05) associated with all renal outcomes except NAG. Finally, in the oldest tertile of workers, associations between lead dose and NAG were unchanged, but fewer associations between the lead biomarkers and the clinical renal outcomes remained significant (p ≤ 0.05) after adjustment for uric acid. In conclusion, our data suggest that older workers comprise a susceptible population for increased uric acid due to lead. Uric acid may be one, but not the only, mechanism for lead-related nephrotoxicity.
KW - Kidney function
KW - Mechanisms
KW - Occupational lead exposure
KW - Renal early biologic effect markers
KW - Uric acid
UR - http://www.scopus.com/inward/record.url?scp=12744269258&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12744269258&partnerID=8YFLogxK
U2 - 10.1289/ehp.7317
DO - 10.1289/ehp.7317
M3 - Article
C2 - 15626645
AN - SCOPUS:12744269258
SN - 0091-6765
VL - 113
SP - 36
EP - 42
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 1
ER -