Transport of Perfluoroalkyl Substances (PFAS) by Three Renal Transporters: Implications for PFAS Bioaccumulation
Shan Niu1,2, Yifei Ma2, Arundhati Tewari2
1Advanced Interdisciplinary Institute of Environment and Ecology, Guangdong Provincial Key Laboratory of Wastewater Information Analysis and Early Warning, School of Technology for Sustainability, Beijing Normal University, Zhuhai 519087, China.
Abstract:
The long biological half-lives of per- and polyfluoroalkyl substances (PFAS) in humans have been linked to interactions with renal transport proteins and polypeptides. However, only a limited number of kidney transporters have been studied for their ability to transport specific PFAS. Moreover, few studies have investigated whether PFAS alternatives serve as substrates for these transporters. In this study, we focused on one renal influx transporter, organic anion transporter 1 (OAT1) and two efflux transporters (P-glycoprotein (P-g) and breast cancer resistance protein (BCRP)) involved in PFAS excretion. We evaluated two well-studied PFAS, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), along with two current substitutes. Hexafluoropropylene oxide dimer acid (HFPO-DA), the major component of the PFOA alternative GenX, was not transported by any of the studied renal transporters. In contrast, hexafluoropropylene oxide trimer acid (HFPO-TA), a minor component of GenX, as well as PFOA itself, were taken up by all studied transporters. Both PFOS and its tested alternative (F53B), including both major and minor components, were substrates of all tested renal transporters, with PFOS and F53B showing relatively higher transport activity. BCRP- and P-gp-mediated transport of five PFAS underwent a saturable process with Michaelis constant (K m) ranging from 1.29 to 7.92 μmol/L and 1.41 to 2.78 μmol/L, respectively. The highest V max/K m ratio was observed for PFOA transport by P-gp (279 pmol/mg protein/min/(μmol/L)). To the best of our knowledge, this is the first study reporting interactions between renal transporters and these legacy PFAS replacements. These findings enhance our understanding of PFAS bioaccumulation at the cellular and molecular levels, offering key parameters for PFAS toxicokinetic modeling.
Related Concept Videos
Drug Elimination by Renal Route: Tubular Secretion
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Renal Drug Excretion: Tubular Secretion
Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels
One important factor is the drug's molecular size. The kidneys readily excrete smaller molecules below 300 Daltons (Da). On the other hand, molecules weighing between 300 and 500 Da are excreted through both urine and bile. Larger molecules above 500 Da tend to be excreted less...
Hepatic Drug Clearance: Role of Transporters
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion, mediated...


