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Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?
Citation:
Weaver, V., D. Kotchmar, J. Fadrowski, AND E. Silbergeld. Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment? Journal of Exposure Science and Environmental Epidemiology . Nature Publishing Group, London, Uk, 26:1-8, (2015).
Impact/Purpose:
The use of biomarkers is now routine in environmental and occupational epidemiology research. However, recent nephrotoxicant research using biomarkers has reported a range of unexpected findings in different populations with different exposures. In this review, we seek to summarize potential explanations for these findings. We also discuss the impact which, depending on the ultimate mechanism(s) involved, may not be limited solely to the nephrotoxicant research arena. For example, if kidney filtration in the normal range alters biomarker levels, misclassification bias would result since biomarkers would reflect kidney function as well as exposures or early biological effects. Our final goal is to present recommendations for future research to elucidate the processes responsible for the unexpected results observed to date.
Description:
Biological monitoring has become a standard approach to exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. Recently, nephrotoxicant research using biomarkers has reported several unexpected findings including: 1) blood and urine toxicant associations with estimated glomerular filtration rate (eGFR) in opposition directions; 2) positive associations between urine toxicant levels and eGFR (in a direction opposite of that expected in nephrotoxicity); and, 3) associations with measured but not predicted toxicant levels in models of eGFR. When considered together, these results may reflect an impact of kidney filtration or processing on biomarker levels. This is more commonly raised in the context of decreased kidney excretion, e.g., reverse causality, however recent data suggest the normal kidney filtration range may be involved as well. Misclassification bias would result if biomarkers reflect kidney function as well as exposures or early biological effects. Furthermore, urine biomarker associations with eGFR that vary by approach used to adjust for urine concentration have also been reported. Urine creatinine, although commonly used for this adjustment, may also reflect kidney processing and could potentially alter observed associations. Future research to address these concerns involves a range of approaches to study design, exposure and outcome assessment, and adjustment for urine concentration.
