Kidney Week

Abstract: PUB576

Modulating Branched-Chain Amino Acid Catabolism: A New Approach to Ameliorate Cisplatin- and Unilateral Ureteral Obstruction (UUO)-Induced Kidney Injury

Session Information

• Publication Only

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Sone, Hisakatsu, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Hisakatsu Sone, PhD

• Lee, Byung Rho, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Byung Rho Lee, PhD

• Vitale, Samuel Vincent, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Samuel Vincent Vitale

• Heo, Dan, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Dan Heo, PhD

• Kwon, Sang-Ho, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Sang-Ho Kwon, MS, PhD

Background

Cisplatin chemotherapy can lead to chronic kidney disease in cancer patients. We have identified that endogenous renal microRNA-messenger RNA (miRNA-mRNA) interactions mediate attenuation of branched-chain amino acid catabolism in cisplatin-induced kidney injury. This study examines the roles of branched-chain amino acid catabolism in maladaptive cellular processes associated with cisplatin nephrotoxicity and unilateral ureter obstruction (UUO) injury.

Methods

To understand the role of BCAA catabolism in the murine models of kidney injury, we conducted marker analyses for renal fibrosis and ferroptosis.

Results

Enhancing branched-chain amino acid catabolism reduces renal ferroptosis and fibrosis in cisplatin- and UUO-induced kidney injury.

Conclusion

Our study reveals a novel regulatory interaction between BCAA catabolism and ferroptosis in proximal tubule cells, as well as fibrosis in chronically injured kidneys. Modulating the BCAA pathway could offer therapeutic potential for alleviating kidney injury caused by cisplatin and UUO.

Funding

• NIDDK Support