Table 2.

Studies (1990–2018) investigating the pharmacokinetic role of the kidneys in metabolism, tissue distribution, or clearance and elimination of per- and polyfluoroalkyl substances in humans

AuthorsYearExposurePharmacokinetic PropertiesMajor Findings
Beesoon et al. (28)2015PFOA, PFOSProtein-binding; eliminationKey differences in protein-binding, volume of distribution, and kidney clearance related to different PFAS isomeric forms
Fàbrega et al. (29)2013PFOA, PFOSVolume of distribution; tissue concentrationsTissue concentration varied by organ (liver>plasma>kidney)
Model-based predictions underestimate actual kidney concentrations
Fu et al. (30)2016PFOA, PFOS, PFHxAEliminationHighlighted possible nonkidney elimination pathways;
t1/2 (by daily clearance rates) ranged from 4.1 to 14.7 yr;
t1/2 (by annualized decline rates) ranged from 1.7 to 3.6 yr
Harada et al. (31)2005PFOA, PFOSEliminationKidney clearance one fifth of the total clearance
No observed sex differences in rate of clearance
Ingelido et al. (32)2018PFBA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUdA, PFDoA, PFBS, PFHxS, PFOSEliminationElimination not mediated by OATP1A2 proximal tubule transporter
Olsen et al. (33)2007PFOA, PFOS, PFHxS Eliminationt1/2 ranged from 3.8 to 8.5 yr
Kidney clearance effected by isomeric forms
Pan et al. (34)201724 target PFASs, including Cl-PFESAProtein-binding; volume of distributionPlacental transfer with high cord sera concentrations
Higher placental transfer efficiencies associated with lower eGFR
Pérez et al. (35)2013PFOA, PFOS, PFBS, PFHxAVolume of distribution; tissue concentrationsTissue concentration varied by organ, with PFBS, PFDoDA, and PFDA demonstrating highest concentrations in the kidneys
Russell et al. (36)2015PFOAEliminationt1/2 was 2.4 yr, slightly longer for men compared with women
Elimination occurred almost exclusively by the kidneys
Shi et al. (37)2016Cl-PFESAEliminationSuggest Cl-PFESA is most bio-persistent known PFAS in humans, with median t1/2 for kidney clearance of 280 yr and total body elimination of 15.3 yr
Worley et al. (38)2017PFOAMetabolism; eliminationGlomerular filtration and active reabsorption and secretion by the proximal tubules via basolateral (via OAT1 and OAT3) and apical (via OAT4 and URAT1) uptake transporters
Yang et al. (39)2010PFOAEliminationActive reabsorption and secretion by the proximal tubules via apical OAT4 and URAT1; proximal tubular handling affected by extracellular pH and isomeric forms
Zhang et al. (40)2013PFOA, PFOSEliminationKey differences in kidney clearance related to different isomeric forms, including chain length, branched versus linear, and functional groups
  • PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate; PFAS, per- and polyfluoroalkyl substances; PFHxA, perfluorohexanoic acid; PFBA, perfluorobutyrate; PFHpA, perfluoroheptanoic acid; PFNA, perfluorononanoic acid; PFDA, perfluorodecanoic acid; PFUdA, perfluoroundecanoic acid; PFDoA, perfluorododecanoic acid; PFBS, perfluorobutane sulfonate; PFHxS, perfluorohexane sulfonate; OATP1A2, organic anion transporting polypeptide 1A2; Cl-PFESA, chlorinated polyfluoroalkyl ether sulfonic acid; PFDoDA, perfluorododecanoic acid; OAT1, organic anion transporter 1; OAT3, organic anion transporter 3; OAT4, organic anion transporter 4; URAT1, urate transporter 1.