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Environmental And Genetic Risk Factors For Renal Function Decline

Asan, South Korea


End stage renal disease (ESRD) is associated with substantial morbidity and mortality. Strategies to prevent the renal function decline that can ultimately result in ESRD are essential. The impact of environmental exposures has received relatively little attention in this regard, despite the fact that exposures such as cadmium and lead are known renal toxicants that are stored long-term in the body and ubiquitous in humans. Therefore, this study is investigating a broad set of causes of renal function decline, including lead, cadmium, and genetic polymorphisms while controlling for other known renal risk factors such as blood pressure, diabetes, nephrotoxic medication use, and age. We are continuing to study a large cohort of current and former lead workers and participants without occupational lead exposure from an earlier grant. Study subjects have a wide range of lead exposure and dose measures and renal outcome data from three visits each over an average of 2.2 years.

Analysis of existing data to date has revealed evidence of longitudinal decline in renal function associated with lead dose measures; interaction between age and lead dose on renal function and renal function decline; interaction between ALAD and VDR genotypes and lead dose on renal function; and associations of environmental level cadmium dose with elevated NAG in a subset of lead workers.

The current study will include 675 participants from the original cohort and enroll 225 new current or former lead workers over age 45 years, those at greater risk for renal function decline. We will characterize cumulative cadmium dose in all participants, measure additional genotypes (ACE and VDR FokI), and extend the follow-up period. We will also obtain blood and tibia lead, BUN, serum creatinine, measured and calculated creatinine clearances, NAG and RBP during 3 evaluations at yearly intervals. The specific aims are to determine: 1) if lead and cadmium dose are or continue to be associated with renal function at cross-section and longitudinally; 2) if there is effect modification by lead or cadmium dose, respectively, on associations between cadmium or lead dose and renal function decline; 3) if hypertension modifies the relations of lead or cadmium dose with renal function decline; and 4) whether polymorphisms in the genes for ALAD, VDR, ACE, and eNOS modify or continue to modify relations of lead and/or cadmium dose with renal outcomes.


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  • Asan, South Korea - selected city