A Sensitive Nephrotoxicity Assay of in vitro Podocyte Effacement

Podocytes are specialised epithelial cells in the kidney glomerulus that have long finger-like processes which wrap around blood vessels to form a size-selective sieve.

This sieve allows ions, water and other small molecules to pass through, while retaining large molecules, including albumin, in the blood. Damage to this glomerular filtration barrier (GFB) due to drug-induced injury or disease, can make the holes in the sieve larger, allowing bigger molecules to pass,  and in turn causing damage further down the kidney tubules. However, not all injury causes podocytes loss; often small morphological changes occur where the foot processes retract (effacement).

We previously developed a primary podocyte FITC-dextran assay that enabled us to assess drug candidates for their ability to make the holes in the GFB larger, but we now wanted to develop an assay to monitor the small morphological changes; an assay for effacement. For this we used high content imaging.