A State-of-the-Science Review of Interactions of Per- and Polyfluoroalkyl Substances (PFAS) with Renal Transporters in Health and Disease: Implications for Population Variability in PFAS Toxicokinetics.
Journal
Environmental health perspectives
ISSN: 1552-9924
Titre abrégé: Environ Health Perspect
Pays: United States
ID NLM: 0330411
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
medline:
10
7
2023
pubmed:
7
7
2023
entrez:
7
7
2023
Statut:
ppublish
Résumé
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and have been shown to cause various adverse health impacts. In animals, sex- and species-specific differences in PFAS elimination half-lives have been linked to the activity of kidney transporters. However, PFAS molecular interactions with kidney transporters are still not fully understood. Moreover, the impact of kidney disease on PFAS elimination remains unclear. This state-of-the-science review integrated current knowledge to assess how changes in kidney function and transporter expression from health to disease could affect PFAS toxicokinetics and identified priority research gaps that should be addressed to advance knowledge. We searched for studies that measured PFAS uptake by kidney transporters, quantified transporter-level changes associated with kidney disease status, and developed PFAS pharmacokinetic models. We then used two databases to identify untested kidney transporters that have the potential for PFAS transport based on their endogenous substrates. Finally, we used an existing pharmacokinetic model for perfluorooctanoic acid (PFOA) in male rats to explore the influence of transporter expression levels, glomerular filtration rate (GFR), and serum albumin on serum half-lives. The literature search identified nine human and eight rat kidney transporters that were previously investigated for their ability to transport PFAS, as well as seven human and three rat transporters that were confirmed to transport specific PFAS. We proposed a candidate list of seven untested kidney transporters with the potential for PFAS transport. Model results indicated PFOA toxicokinetics were more influenced by changes in GFR than in transporter expression. Studies on additional transporters, particularly efflux transporters, and on more PFAS, especially current-use PFAS, are needed to better cover the role of transporters across the PFAS class. Remaining research gaps in transporter expression changes in specific kidney disease states could limit the effectiveness of risk assessment and prevent identification of vulnerable populations. https://doi.org/10.1289/EHP11885.
Sections du résumé
BACKGROUND
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and have been shown to cause various adverse health impacts. In animals, sex- and species-specific differences in PFAS elimination half-lives have been linked to the activity of kidney transporters. However, PFAS molecular interactions with kidney transporters are still not fully understood. Moreover, the impact of kidney disease on PFAS elimination remains unclear.
OBJECTIVES
OBJECTIVE
This state-of-the-science review integrated current knowledge to assess how changes in kidney function and transporter expression from health to disease could affect PFAS toxicokinetics and identified priority research gaps that should be addressed to advance knowledge.
METHODS
METHODS
We searched for studies that measured PFAS uptake by kidney transporters, quantified transporter-level changes associated with kidney disease status, and developed PFAS pharmacokinetic models. We then used two databases to identify untested kidney transporters that have the potential for PFAS transport based on their endogenous substrates. Finally, we used an existing pharmacokinetic model for perfluorooctanoic acid (PFOA) in male rats to explore the influence of transporter expression levels, glomerular filtration rate (GFR), and serum albumin on serum half-lives.
RESULTS
RESULTS
The literature search identified nine human and eight rat kidney transporters that were previously investigated for their ability to transport PFAS, as well as seven human and three rat transporters that were confirmed to transport specific PFAS. We proposed a candidate list of seven untested kidney transporters with the potential for PFAS transport. Model results indicated PFOA toxicokinetics were more influenced by changes in GFR than in transporter expression.
DISCUSSION
CONCLUSIONS
Studies on additional transporters, particularly efflux transporters, and on more PFAS, especially current-use PFAS, are needed to better cover the role of transporters across the PFAS class. Remaining research gaps in transporter expression changes in specific kidney disease states could limit the effectiveness of risk assessment and prevent identification of vulnerable populations. https://doi.org/10.1289/EHP11885.
Identifiants
pubmed: 37418334
doi: 10.1289/EHP11885
pmc: PMC10328216
doi:
Substances chimiques
perfluorooctanoic acid
947VD76D3L
Fluorocarbons
0
Alkanesulfonic Acids
0
Environmental Pollutants
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
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