TJ0113 alleviates ferroptosis by improving mitochondria of renal tubules in the transition from AKI to CKD

Acute kidney injury (AKI) is a prevalent clinical complication with a high risk of progression to chronic kidney disease (CKD), yet effective drugs to prevent or treat the transition from AKI to CKD are still lacking. The kidney is an organ rich in mitochondria and mitochondrial dysfunction plays a pivotal role in the progression from AKI to CKD. In this study, we established a mouse model of bilateral renal artery ischemia-reperfusion injury to investigate whether TJ0113, a mitophagy inducer currently in Phase 2 of clinical trials (NCT06596005), can be used to mitigate the transition from AKI to CKD. We found that TJ0113 improved the high mortality rate and renal dysfunction in AKI mice, alleviated renal injury, inflammation, and interstitial fibrosis during the transition from AKI to CKD, and improved mitochondrial quality in renal tubules. RNA-seq results showed that TJ0113 reduced the expression of activating transcription factor 3 (ATF3), which is upstream of the classic ferroptosis pathway. In summary, our data show that TJ0113 maintains mitochondrial quality in renal tubules through mitophagy, thereby improving the progression from AKI to CKD, and represents a potential drug for preventing and treating the transition from AKI to CKD.