Expression of drug transporters in human allogenic transplanted kidneys in acute rejection.

Kidney drug transporters, primarily located in the basolateral and apical membranes of proximal tubule cells, play a key role in the secretion and reabsorption of drugs and endogenous compounds. Recent studies have demonstrated that kidney diseases can alter transporter expression; however, the expression of these transporters in human transplanted kidneys, with and without rejection, remains unclear. Therefore, the aim of this study was to investigate the mRNA expression (qRT-PCR) and immunolocalization (via immunohistochemistry) of key ABC (ATP-binding cassette) (n = 14) and SLC (solute carriers) (n = 33) transporters in glomeruli and proximal tubule cells from human normal kidney (CTRL, n = 8), non-rejected transplanted kidney (AR-0, n = 7) and transplanted kidney under rejection process (AR-I, n = 8) from patients receiving immunosuppressive drugs. Our study shows that mRNA expression level of SLC22A4, SLC22A6, SLC22A7, SLC22A8, SLC28A1, SLC47A1, SLC22A11, SLC15A2, SLC16A1, ABCC2, ABCC5 and ABCC6 are statistically significantly downregulated, while SLC22A2, SLCO4A1 and ABCB1 are statistically upregulated in proximal tubule cells from rejected transplanted kidneys compared to controls. Immunohistochemistry revealed that OAT1, OAT3, OCT2, MATE1, MRP2, MRP6 and P-gp were primarily expressed in proximal tubule cells, with significantly lower protein expression of OAT1, OAT3, P-gp in AR-I and AR-0 biopsies compared to CTRL sections. These preliminary data suggest that the expression profile of kidney transporters may be altered in transplanted kidneys from patients treated with immunosuppressive drugs.