Abstract: SA-PO1273
Sex-Based Differences in Cisplatin-Induced Nephrotoxicity: Divergent Immunological and Pathological Responses
Session Information
- Onconephrology: Epidemiological Trends, Risk Stratification, and Clinical Outcomes
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Sanchez Vega, Dianet, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Weis, Theresa A., University of Louisville School of Medicine, Louisville, Kentucky, United States
- O'Steen, Barbara, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Siskind, Leah J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Beverly, Levi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
Cisplatin is a potent chemotherapeutic agent, but its efficacy is limited by dose-dependent nephrotoxicity, with 30% of patients developing kidney injury, subsequently increasing the risk of chronic kidney disease. Sex-based differences are implicated as a biological variable of cisplatin-induced nephrotoxicity (CIN) and in immunological responses but are greatly understudied. Given the crucial role of the immune system in mediating CIN, we hypothesize that sex-based immunological variations contribute to differential susceptibility to CIN.
Methods
Male and Female 8-week-old B6:129 mice were treated with weekly cisplatin (7mg/kg), or vehicle control dosing for 4 weeks. Following the final cisplatin injection, kidney function (transdermal GFR measurements, BUN), immune profile (Flow cytometry), injury (Urinary NGAL, KIM-1 expression), fibrosis (Picorious Sirius red stain), inflammation ( Western blot , PCR) and pathology ( PAS stain , SR stain and pathologist scoring) were assessed. Statistical Analysis was performed using Two- Way-ANOVA, with P < 0.05 considered statistically significant.
Results
Cisplatin treatment increased kidney fibrosis and altered kidney function in both sexes. Male mice exhibited significant increase in Kidney Injury Marker-1 (KIM-1) and kidney leukocytes, including resident and infiltrating macrophages. Conversely, treated females presented a less significant increase in kidney injury marker-1 and kidney leukocytes. Additionally, there were pathological differences in the location of injury along the nephron. Despite these immunological and pathological differences, cisplatin induced an equivalent decrease in kidney function in both treated sexes.
Conclusion
Data indicate that kidney function in females could be deteriorated through a different mechanism than in males and despite differences in immunological responses to cisplatin. This study highlights the importance of considering sex as a biological variable in CIN and advocates for sex specific strategies to mitigate these adverse effects. Further studies will aid in gaining mechanistic insight for these sex specific differences for the development of more effective treatments.
Funding
- Other NIH Support