Lay summary
Acute kidney injury, caused by various insults including bacterial and viral (COVID19) infections, nephrotoxic drugs, and reduced blood flow, is associated with significant mortality and risk of developing chronic kidney disease. We have a limited understanding of the processes of injury and repair in AKI, although DNA damage to kidney cells has emerged as a key factor. New targeted therapies are urgently needed. We address these shortcomings in this proposal with our novel discovery that CDKL5, belonging to a druggable class of enzymes called kinases, is linked to DNA repair during AKI. We have identified some candidate inhibitors of CDKL5 and propose conducting preclinical testing of these using human kidney organoids (small balls of kidney tissue made from stem cells) and a mouse model of AKI. This work holds the promise of developing the world's first targeted drug therapy for AKI, which in the era of COVID19 is urgently needed.