The aProximateTM model for renal drug safety/efficacy and transporter studies

The proximal tubules of the kidney nephron play a key role in the reabsorption of filtered amino acids, glucose, solutes, and low molecular weight proteins, such as albumin, from the tubular filtrate. Many xenobiotics are also reabsorbed here, which if not rapidly cleared from the cells, can cause nephrotoxicity.

The large number of drug transporters and receptors expressed in proximal tubule cells (PTCs) give them their absorptive and secretory functions. Two key endocytic receptors strongly expressed on the apical surface of these cells are megalin and cubilin, which play an important role in reabsorption of large molecules and glomerular-filtered proteins (Fig. 1). We have recently developed a live cell high content imaging assay to monitor the uptake of fluorescently labelled proteins, as well as large molecules, including oligonucleotides, aminoglycosides, and antibody-drug conjugates via this endocytic uptake mechanism.