Understanding PFAS Interactions with Kidney Function in Health and Disease

Per- and polyfluoroalkyl substances (PFAS) are a class of thousands of chemicals widely used in personal, household, commercial, and industrial applications. Their broad use and high stability has led to their being detected throughout the environment and within humans on a global scale. Previous studies have revealed associations between exposure to specific PFAS and health effects including reduced immune function, liver disease, kidney disease, and adverse reproductive and developmental outcomes. Elimination through urine is critical to determining the total body clearance of PFAS, and has been connected to the function of a number of kidney transporters. A recent study suggested that the half-life of perfluorooctanoic acid (PFOA), one particularly toxic PFAS, that had been established in humans was too long. This claim was based on a single study on patients with advanced cancer. However, a major problem in this study is that they did not consider the influence of disease on PFOA elimination. This is important because kidney transporter protein levels can be significantly altered in humans with kidney disease (e.g., chronic renal failure, acute renal failure, and acute kidney injury), which can strongly influence PFAS elimination from the human body. Therefore, it remains unclear how kidney transporter expression and changes that result from disease could impact elimination of PFAS in humans. In this study, we propose to combine data on transporter expression under different states with in vitro transporter experiments to evaluate how differences in kidney transporter expression in health and disease could impact the elimination rate, and thereby the biological half-lives, of PFAS in humans. This work will provide critical data for setting evidence-based health advisory limits for these ubiquitous chemicals and identifying particularly sensitive populations