title: Associations among lead dose biomarkers, uric acid, and renal function in Korean lead workers.
abstract: 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-ss-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 microg/g bone mineral, and 32.0 +/- 15.0 microg/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 (ss = 0.0111, p < 0.01 and ss = 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 (ss = 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 less than or equal to 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.
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Weaver
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Todd
authors.forename: Kyu-Dong
authors.initials: KD
authors.lastname: Ahn
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology; D007723:Korea; D007854:Lead / Q000097:blood*; D007855:Lead Poisoning / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D014527:Uric Acid / Q000009:adverse effects* / Q000032:analysis
chemical_list: D015415:Biomarkers; D014527:Uric Acid; D007854:Lead; D003404:Creatinine