Abstract

High Content Imaging in Chronic Kidney Disease

Douglas Ross-Thriepland, Senior Scientist, Astrazeneca

Diabetic nephropathy is the world’s leading and most rapidly growing cause of end stage renal disease (ESRD), with up to 40 % of all diabetic patients developing kidney damage. The common manifestation of chronic kidney disease (CKD) is tubulointerstitial fibrosis and is characterised by progressive scaring and loss of kidney function. Through employing a combination of phenotypic screening and high content imaging we aimed to identify novel targets and compounds that will halt or slowdown disease progression in patients with moderate to severe CKD. To achieve this we built a phenotypic screen using human primary cells that paralleled the in vivo disease state of kidney myofibroblast activation, the cell type responsible for driving renal scarring. By screening a focused phenotypic compound set we have identified multiple targets that abrogate the activation of kidney myofibroblast cells and present exciting new drug targets that are being progressed.