Introduction and Objective: The AKI-to-CKD transition lacks effective therapies. Cathepsin L (CTSL), a protease involved in renal fibrosis, is a potential target. This study determined whether CTSL inhibition alleviates progression in a murine IR injury model. Methods: 8-week-old male C57BL/6J mice received a CTSL inhibitor (998, 10mg/kg/day) or vehicle by oral gavage, starting 2 days before injury. On Day 0, unilateral left renal ischemia was induced by pedicle clamping for 28 minutes. Contralateral nephrectomy was performed on Day 13 to accelerate progression. Mice were sacrificed on Day 14 for collection of serum, urine, and kidney tissue. We assessed serum creatinine (SCr), urine albumin-to-creatinine ratio (UACR), and kidney histology (injury, fibrosis). Statistics used unpaired t-test. Results: The inhibitor group showed significantly lower SCr (81.93±10.70 vs. 112.0±21.60 umol/L, p0.01) and UACR (108.2±12.65 vs. 174.4±18.00 μg/g, p0.01) versus vehicle. Histology confirmed reductions in tubular injury, inflammation, and interstitial fibrosis. Conclusion: Pharmacological CTSL inhibition significantly improved functional outcomes and alleviated structural outcomes in a mouse model of IR-induced AKI-to-CKD progression, identifying CTSL as a promising therapeutic target. Disclosure Y. Wang: None. Y. Xu: None. F. Shen: None. J. Yang: None.
WANG et al. (Fri,) studied this question.