Purpose: Chronic occupational exposure to lead is related to low urate excretion and a high incidence of gout in lead workers. However, whether chronic low-level environmental lead exposure influences urate excretion in the general population remains unknown.
Subjects and methods: We studied 111 healthy subjects with normal renal function (serum creatinine level < or =1.4 mg/dL) and no previous lead exposure or systemic diseases. All subjects had their blood lead levels measured, received ethylenediaminetetraacetic acid mobilization tests to assess their body lead burdens, and were investigated for renal function and urate excretion to assess the relation between lead and urate excretion. We studied urate excretion before and after lead chelation therapy in 24 subjects with high-normal body lead burden (>78 mg and <600 mg).
Results: Healthy subjects with gout (n = 27) manifested a higher body lead burden (84 +/- 42 mg vs. 45 +/- 30 mg, P <0.0001) and lower urate clearance (3.7 +/- 1.2 mL/min/1.73 m(2) vs. 6.0 +/- 2.8 mL/min/1.73 m(2), P <0.0001) than did those without gout (n = 84). Blood lead levels and body lead burden of all subjects were within the safe range. In analyses that adjusted for age, sex, body mass index, protein intake, and creatinine clearance, blood lead level was significantly related to serum urate level (beta coefficient [+/- SE] = 0.23 +/- 0.11, P = 0.03), and body lead burdens were related to all indices of urate excretion (serum urate: beta coefficient = 0.023 +/- 0.005, P <0.0001; daily urate excretion: beta coefficient = -1.55 +/- 0.40, P = 0.0002; urate clearance: beta coefficient = -0.030 +/- 0.006, P <0.0001; fractional urate excretion: beta coefficient= -0.034 +/- 0.006, P <0.0001). Following lead chelation therapy, urate clearance increased after body lead burden was reduced (3.4 +/- 1.2 mL/min/1.73 m(2) vs. 4.9 +/- 1.4 mL/min/1.73 m(2), P <0.005).
Conclusion: Chronic low-level environmental lead exposure may inhibit urate excretion in the general population, and lead chelation therapy reduces this inhibition. These findings support efforts to reduce sources of environmental lead exposure and suggest alternative approaches to hyperuricemia and gout in the general population.