Opportunity: Kidney Transporter Expression Data to be Integrated

[prvmalik]

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.

[PavelBal]

Maybe move the issue to this repository: https://github.com/Open-Systems-Pharmacology/Protein-Abundance-Database

that it will not get lost between PK-Sim bug reports?