Table 3.
Studies that address the relationship between cellular efflux transporters and uremic toxins in chronic kidney disease.
| Protein | Experimental Model | Main Findings |
|---|---|---|
| MATE1 | HEK293 cells | Creatinine and guanidine as substrates [159] |
| HEK293 cells | Creatinine as substrate [161] | |
| MDCKII and HEK cells | Transport of TMAO, which was suppressed by trimethoprim [125] | |
| Nephrectomized rats | Decreased protein levels in the kidneys [164] | |
| MATE2-K | HEK293 cells | Creatinine and guanidine as substrates [159] |
| BCRP | ciPTEC cells | BCRP inhibition increased intracellular PCS levels [174] |
| HeLa cells | TMAO transport [110] | |
| Membrane vesicles from MRP4-overexpressing HEK cells | Inhibited by hippuric acid, IS, and kynurenic acid [178] | |
| Caco-2 cells | Urate transport. IS reduced BCRP expression [179] | |
| Endothelial cells | Uric acid decreased the BCRP protein levels [183] | |
| Abcg2-knockout mice with adenine-induced CKD and membrane vesicles from HEK293A cells | Increased plasma levels and decreased renal elimination of IS. In vitro, IS transport [175] | |
| Abcg2-knockout mice and HEK293 cells | Kynurenic acid as substrate [177] | |
| Abcg2-knockout mice | Increased plasma levels and low urine levels of IS [175] | |
| Adenine-induced acute renal failure rats | Febuxostat, an BCRP inhibitor, decreased renal clearance of the IS [97] | |
| Nephrectomized rats | Decreased mRNA levels in the kidney [172] | |
| Nephrectomized rats | Decreased protein and mRNA levels in the kidney [173] | |
| MRP2 | HeLa cells | Performs cellular efflux of TMAO [110] |
| Nephrectomized rats | Increased protein and mRNA levels in the kidneys [84] | |
| Nephrectomized rats | Increased mRNA levels in the liver and the kidneys [172] | |
| Nephrectomized rats | Decreased protein levels in the intestine [188] | |
| MRP4 | Membrane vesicles from MRP4-overexpressing HEK cells | Inhibited by IS, hippuric acid, kynurenic acid, IAA, and phenylacetic acid [178] |
| ciPTEC cells | Inhibited by PCS and p-cresyl glucuronide [174] | |
| HeLa cells | Performs cellular efflux of TMAO [110] | |
| Nephrectomized rats | Increased protein and mRNA levels in the kidneys [84] | |
| Nephrectomized rats | No differences in mRNA levels in the kidney, liver, and intestine [172] | |
| Nephrectomized rats | No differences in mRNA levels in the kidney and the liver [189] |
Abbreviations: ciPTEC, immortalized renal proximal tubule epithelial cells; HEK, human embryonic kidney cells; HRPTEC, human renal proximal tubule epithelial cells; IAA, indole-3-acetic acid; IS, indoxyl sulfate; MDCKII, Madin–Darby canine kidney II cells; PCS, p-cresyl sulfate; TMAO, trimethylamine-N-oxide.