Targeting IRAP as a novel strategy to reduce renal fibrosis and injury in chronic kidney disease

New strategies are needed to combat pathological organ fibrosis, leading to end stage organ failure. We have identified the enzyme insulin regulated aminopeptidase (IRAP), as one such promising new target. This study compared the anti-fibrotic efficacy of novel IRAP inhibitors, against the current gold standard treatment, Perindopril. Additionally, we investigated the role of IRAP substrates in mediating reno-protective effects. These findings provide proof-of-concept that IRAP inhibition mediates anti-fibrotic and anti-inflammatory effects in renal fibrosis. Furthermore, the reno-protective effect was greater than that achieved using an ACE inhibitor and involved multiple IRAP substrates, highlighting a multi-modal mechanism of action of IRAP inhibition.