2. Academic Validation
  3. Bardoxolone methyl improves survival and reduces clinical measures of kidney injury in tumor-bearing mice treated with cisplatin

Bardoxolone methyl improves survival and reduces clinical measures of kidney injury in tumor-bearing mice treated with cisplatin

  • AAPS Open. 2025:11:6. doi: 10.1186/s41120-025-00107-5.
Lauren E Thompson 1,  Stacey M Tuey 1,  Paola Garcia Gonzalez 1,  Carly S Chesterman 1,  Courtney D McGinnis 1,  M Scott Lucia 2,  Lauren M Aleksunes 3 4,  Charles L Edelstein 5,  Melanie S Joy 1 5 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • 2 Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • 3 Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA.
  • 4 Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
  • 5 Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • 6 University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
PMID: 40881130 DOI: 10.1186/s41120-025-00107-5
Abstract

Objective: Acute kidney injury (AKI) occurs in approximately one-third of patients treated with cisplatin and there is an outstanding need for mitigation strategies to decrease the frequency and severity of cisplatin-induced AKI. This study evaluated bardoxolone methyl (BARD) as a nephroprotectant in a multidose, tumor-bearing mouse model of cisplatin-induced AKI. BARD is an attractive therapeutic intervention due to its ability to protect against cisplatin-induced nephrotoxicity by activating Nrf2 and previous reports suggesting anti-tumorigenic effects.

Methods: In this study, CMT167 tumor-bearing mice were treated with four weekly doses of cisplatin with or without BARD and evaluated for survival, tumor growth, and clinical and histological measures of AKI. Kidney injury and/or function were evaluated by quantification of urinary kidney injury molecule-1 (KIM-1) and serum creatinine (SCr) levels as well as histopathology.

Results: Compared to mice receiving cisplatin alone, co-treatment with BARD significantly enhanced survival (p = 0.01). Moreover, BARD prevented elevation of urinary KIM-1 concentrations as early as one week after cisplatin treatment (p < 0.01) - a response that was observed throughout the 4-week study period. Cisplatin increased SCr concentrations by four weeks, which was prevented by BARD co-administration (p < 0.01). Cisplatin treatment significantly decreased tumor burden compared to vehicle-treated mice (p < 0.05 after two cisplatin doses) - a response that was not altered by BARD co-treatment.

Conclusions: Overall, the results of this study demonstrate that BARD has the potential to improve survival and reduce clinical measures of kidney injury in tumor-bearing mice treated with cisplatin, suggesting it could be used as a nephroprotectant to mitigate cisplatin-induced AKI.

Keywords

Acute Kidney Injury; Bardoxolone Methyl; Cisplatin; Nephrotoxicity; Nrf2.

Figures
Products