Effects of uremic toxins on renal and hepatic transporters
| Uremic toxins | Total Cmax | Unbound Cmax | OAT1 IC50 | OAT3 IC50 | OATP1B1 IC50 |
|---|---|---|---|---|---|
| 2-Nonenala | 727 µM (Duranton et al., 2012) | 0.7 µM (Hsueh et al., 2016) | IC50: 19 µM for 6-CF uptake (Hsueh et al., 2016) | 60 µM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| 4-Decenala | 650 µM (Duranton et al., 2012) | 0.7 µM (Hsueh et al., 2016) | IC50: 38 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 53 µM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) | 81.1 µM (Fujita et al., 2014) | N/A | IC50: 79 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 28 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 158 µM for SN38 uptake (Fujita et al., 2014) |
| Creatinine | N/A | 1.2 mM (Hsueh et al., 2016) | IC50: 14 mM for 6-CF uptake (Hsueh et al., 2016) | IC50: 40 mM for 6-CF uptake (Hsueh et al., 2016) | IC50: > 10 mM for E13S uptake (Sato et al., 2014) |
| Hippuric acid | 398 µM (Duranton et al., 2012) | 231 (Duranton et al., 2012) | IC50: 31 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 41 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 6.71 mM for SN38 uptake (Fujita et al., 2014) |
| 6-Hydroxyindole | 0.227 µM (Masuo et al., 2020) | N/A | N/A | N/A | IC50: 16.7 (coincubation) IC50: 12.1 (pre- and coincubation) (Masuo et al., 2020) |
| Indole 3-acetic acid | 11.6 µM (Duranton et al., 2012) | 2.11 (Duranton et al., 2012) | IC50: 140 µM for 6-CF uptake (Hsueh et al., 2016) | 38% inhibition for 6-CF uptake by 250 µM (Hsueh et al., 2016) | >3 mM for SN38 uptake (Fujita et al., 2014) 194 µM for SN38 uptake (Katsube et al., 2017) |
| Indoxyl sulfate | 109 µM (Duranton et al., 2012) | 15.1 µM (Duranton et al., 2012) | IC50: 110 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 270 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 2.29 mM for SN38 uptake (Fujita et al., 2014) |
| Indoxyl-β-D-glucuronidea | 9.49 µM (Duranton et al., 2012) | N/A | N/A | IC50: 670 µM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| Kynurenic acida | 0.799 µM (Duranton et al., 2012) | N/A | IC50: 34 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 23 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 180 µM for E13S uptake (Sato et al., 2014) |
| N2,N2-Dimethylguanosine | N/A | 1.3 µM (Hsueh et al., 2016) | no inhibition for 6-CF uptake by 140 µM (Hsueh et al., 2016) | IC50: 140 µM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| Nonanal | 0.485 µM (Duranton et al., 2012) | 0.5 µM (Hsueh et al., 2016) | IC50: 22 µM for 6-CF uptake (Hsueh et al., 2016) | 42% inhibition for 6-CF uptake by 50 µM (Hsueh et al., 2016) | N/A |
| p-Cresol | N/A | N/A | N/A | N/A | IC50: 4.6 mM for E13S uptake (Sato et al., 2014) |
| p-Cresyl sulfate | N/A | 211 µM (Hsueh et al., 2016) | IC50: 210 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 200 µM for 6-CF uptake (Hsueh et al., 2016) | 47% inhibition by 1 mM (Masuo et al., 2020) |
| Phenol | 59 µM (Hsueh et al., 2016) | N/A | 31% Inhibition for 6-CF uptake by 6.4 mM (Hsueh et al., 2016) | IC50: 3.1 mM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| Phenylacetic acid | N/A | 3.5 mM (Hsueh et al., 2016) | IC50: 540 µM for 6-CF uptake (Hsueh et al., 2016) | IC50: 1.3 mM for 6-CF uptake (Hsueh et al., 2016) | N/A |
| Uric acid | 383 µM (Duranton et al., 2012) | 500 µM (Hsueh et al., 2016) | IC50: 2.2 mM for 6-CF uptake (Hsueh et al., 2016) | IC50: 670 µM for 6-CF uptake (Hsueh et al., 2016) | N/A |
6-CF, 6-carboxyfluorescein; E3S, estrone-3-sulfate; N/A, not available.
aHighest concentrations of Cmax and unbound Cmax for uremic toxins.