Reference no: EM133535432

Summarize this - data suggest that, at the moderate levels of lead exposure present in our population, older workers comprise a susceptible population for increased uric acid. This is consistent with the published literature, as noted above. The impact of adjustment for renal function and blood pressure suggests that the effect of lead on uric acid may be mediated through these pathways. However, because blood lead remained associated with uric acid in our most susceptible group (the oldest workers who had the greatest renal dysfunction), even after adjustment for renal function and blood pressure, mechanisms other than decreased glomerular filtration, such as decreased tubular secretion or even extrarenal mechanisms, may be involved at these exposure levels. Because our data [and those of others suggest an effect of lead on uric acid beyond that due to renal dysfunction alone, and because uric acid was associated with adverse renal outcomes and resulted in reduced significance of lead biomarker associations in our population, uric acid may be one mechanism through which lead is nephrotoxic. However, this is not the only mechanism for lead-related nephrotoxicity. In our data, the association between blood lead and serum creatinine remained significant (p< 0.05) even after adjustment for uric acid. Associations between lead dose and NAG were unchanged, and uric acid was inversely associated with RBP. The effects of lead and uric acid on the NO system are also different. Thus, other mechanisms must be involved. Conclusions regarding causality in this study must be limited because it is cross-sectional. An additional limitation is that we were not able to adjust for the use of medications that influence uric acid because Koreans are not routinely provided with the names of their medications. However, few participants reported any prescription medication use. Our results do suggest that further evaluation of relations among the lead dose biomarkers, uric acid, and renal function in our longitudinal data set would be of value. This is particularly true because these mechanistic relations may be clinically important. EDTA chelation has been reported to improve both renal function and urate clearance in patients with renal insufficiency and gout, even when EDTA- chelatable lead body burdens were quite low. If this work is replicated in other populations and low-level uric acid is found to be nephrotoxic, uric acid should also be monitored in patients who are in the early stages of diseases such as early chronic renal insufficiency and whose lead body burdens are amenable to chelation.