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
| Authors | Year | Exposure | Pharmacokinetic Properties | Major Findings |
|---|---|---|---|---|
| Beesoon et al. (28) | 2015 | PFOA, PFOS | Protein-binding; elimination | Key differences in protein-binding, volume of distribution, and kidney clearance related to different PFAS isomeric forms |
| Fàbrega et al. (29) | 2013 | PFOA, PFOS | Volume of distribution; tissue concentrations | Tissue concentration varied by organ (liver>plasma>kidney) |
| Model-based predictions underestimate actual kidney concentrations | ||||
| Fu et al. (30) | 2016 | PFOA, PFOS, PFHxA | Elimination | Highlighted 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) | 2005 | PFOA, PFOS | Elimination | Kidney clearance one fifth of the total clearance |
| No observed sex differences in rate of clearance | ||||
| Ingelido et al. (32) | 2018 | PFBA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUdA, PFDoA, PFBS, PFHxS, PFOS | Elimination | Elimination not mediated by OATP1A2 proximal tubule transporter |
| Olsen et al. (33) | 2007 | PFOA, PFOS, PFHxS | Elimination | t1/2 ranged from 3.8 to 8.5 yr |
| Kidney clearance effected by isomeric forms | ||||
| Pan et al. (34) | 2017 | 24 target PFASs, including Cl-PFESA | Protein-binding; volume of distribution | Placental transfer with high cord sera concentrations |
| Higher placental transfer efficiencies associated with lower eGFR | ||||
| Pérez et al. (35) | 2013 | PFOA, PFOS, PFBS, PFHxA | Volume of distribution; tissue concentrations | Tissue concentration varied by organ, with PFBS, PFDoDA, and PFDA demonstrating highest concentrations in the kidneys |
| Russell et al. (36) | 2015 | PFOA | Elimination | t1/2 was 2.4 yr, slightly longer for men compared with women |
| Elimination occurred almost exclusively by the kidneys | ||||
| Shi et al. (37) | 2016 | Cl-PFESA | Elimination | Suggest 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) | 2017 | PFOA | Metabolism; elimination | Glomerular 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) | 2010 | PFOA | Elimination | Active 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) | 2013 | PFOA, PFOS | Elimination | Key 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.