Rucaparib, a US Food and Drug Administration (FDA)-Approved PARP1 Inhibitor, Is Renoprotective Against Ischemic Renal Injury and Progression to CKD

Background: Ischemia/reperfusion injury (IRI) accounts for ~50% of acute kidney injury (AKI) cases and is also a critical contributor to chronic kidney disease (CKD) development. Our prior work has established that overactivation of poly(ADP-ribose) polymerase 1 (PARP1) promotes AKI and CKD through bioenergetic failure, inflammation, and fibrosis. However, a lack of clinically effective PARP inhibitors has hindered translation. Methods: We investigated whether Rucaparib, an FDA-approved PARP inhibitor used in cancer therapy, could be repurposed to protect against renal IRI and its progression to CKD. Mice subjected to 30 min bilateral renal I/R were treated with Rucaparib (10 mg/kg/day, i.p), beginning one day prior to injury. Results: Kidney function was evaluated over several time points (days 1–10) using glomerular filtration rate, serum creatinine, and blood urea nitrogen measurements. Renal I/R caused significant morphological and functional kidney damage. Importantly, administration with Rucaparib preserved GFR at near-baseline levels, reduced serum creatinine and BUN and ATP levels. Additionally, Rucaparib suppressed renal fibrosis, extracellular matrix accumulation, α-smooth muscle actin expression, and inflammatory cell infiltration following I/R. Conclusion: Overall, these findings support the potential of Rucaparib as a promising therapeutic approach for preventing AKI and its progression to CKD.