Opportunity: Kidney Transporter Expression Data to be Integrated

Hi all,

To my knowledge this is the first data that quantifies the expression of transporters in the kidney for all species (Basit et al., 2019, doi: 10.1124/dmd.119.086579). Units are presented in pmol/g kidney. This discovery is a first step toward being able to use in vitro transporter assay data to parameterize tubular secretion in a PBPK model.

Transporter assays are generally conducted using Human Embryonic Kidney cell lines (HEK-293) that have been transfected with one transporter. Cells and the drug are incubated together. After a certain period of time, the cells are lysed and the amount of drug inside the cells is determined. A control of non-transfected HEK-293 cells is used to calculate the contribution of non-specific transport/passive diffusion. Vmax is reported as umol drug transported per mg protein lysate per time.

Questions to be answered:

What is the mg protein lysate per HEK-293 cell? Milo et al., 2013, doi: 10.1002/bies.201300066 suggests 200mg protein per 1 mL cells

What is the number of tubular cells per g kidney? SimCyp has a number of estimates on this, though they vary widely

Then apply 2 assumptions:

The concentration of transporters in a proximal tubule cell in a real kidney is the same as the concentration in a transfected human embryonic kidney cell
The renal transporters are only expressed on the tubular cells of the kidney

As more data becomes available we can challenge these two assumptions, but it's a start.

Open-Systems-Pharmacology / PK-Sim

Opportunity: Kidney Transporter Expression Data to be Integrated #1332