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Virginia M. Weaver,^1,2 Bernard G. Jaar,^2,3 Brian S. Schwartz,^1,2,3 Andrew C. Todd,⁴ Kyu-Dong Ahn,⁵ Sung-Soo Lee,⁵ Jiayu Wen,¹ Patrick J. Parsons,⁶ and Byung-Kook Lee⁵

¹Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA; ²Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; ³Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA; ⁴Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA; ⁵Institute of Industrial Medicine, SoonChunHyang University, Asan, South Korea; ⁶Lead Poisoning/Trace Elements Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA

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 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 (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 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. Key words: kidney function, mechanisms, occupational lead exposure, renal early biologic effect markers, uric acid. Environ Health Perspect 113: 36-42 (2005) . doi:10.1289/ehp.7317 available via http://dx.doi.org/ [Online 30 September 2004]

Address correspondence to B.-K. Lee, Institute of Industrial Medicine, SoonChunHyang University, 646 Eupnae-Ri, Shinchang-Myun, Asan-Si, Choongnam, 336-745 South Korea. Telephone: 82-41-530-1760. Fax: 82-41-530-1778. E-mail: leebkk@asan.sch.ac.kr

We thank Y.-B. Kim, G.-S. Lee, and B.-K. Jang for assistance with data collection in South Korea.

This research was supported by grants ES07198 (B.S.S.) and 2 ES07198 (V.M.W.) from the National Institute of Environmental Health Sciences ; grant KRF-2000-00545 (B.-K.L.) from the Korea Research Foundation ; and the Richard Ross Clinician Scientist Award from the Johns Hopkins University School of Medicine (B.G.J.) .

The authors declare they have no competing financial interests.

Received 8 June 2004 ; accepted 30 September 2004.