Kidney

Renal proximal and distal tubules carry out specialized directional transport of various solutes.Transporters in the kidney mediate the secretion or reabsorption of many compounds and thereby influence the plasma levels of their substrates. P-gp, MRP2, MRP4 and the family of OATs, OCTs, OATPs as well as PEPTs are expressed in the renal epithelial cells to regulate the excretion and the reabsorption of endogenous and exogenous organic anions, cations, peptides and nucleosides that include various kinds of drugs and their metabolites.

P-gp, MRP2, MRP4 primarily localize to the apical (luminal) membrane of renal epithelial cells, while MRP1 and MRP6 have been shown to be expressed on the basolateral membrane.
Members of the OATP, OCT (OCT2) and OAT (OAT1, 3) transporter families have been identified in the basolateral membrane of proximal tubule cells. The two peptide transporters PEPT1 and PEPT2 are present on the luminal membrane of proximal tubule cells and were shown to be responsible for the tubular re-absorption of peptide-like drugs such as beta-lactam antibiotics across the brush-border membranes. The re-absorbtion process results in lower renal clearance than expected based on glomerular filtration. Furthermore, the uptake process might result in increased concentration of drugs in the cytoplasm of proximal tubular cells leading to toxic effects in the kidney. Screening the interaction of test drugs with ABC efflux and uptake transporters is an excellent way to predict active transport involved in their renal elimination.

Localization of efflux and uptake transporters in the kidney proximal tubules

Available assays within the Kidney package

Membrane based HTS efflux transporter assays

Whole cell based HTS transporter assays

Screening strategy

Specific transporter interactions can be characterized with ABC efflux and uptake transporter assays that might shed light on the pharmacokinetics of the test compound in the kidney proximal tubules.