Nephrology & Therapeutics

Biography

Biography: Christine N Metz

Abstract

Cisplatin is a potent chemotherapy for treating ovarian and other cancers. Cisplatin-induced acute kidney injury (AKI) occurs in ~25% of patients, while hypomagnesemia occurs in 90% of patients. Previous studies have implicated magnesium (Mg) status in cisplatin-induced AKI. We explored the effect of Mg deficiency (MgD) (±Mg supplementation, MgS) in a mouse model of cisplatin-induced AKI. In addition, using an ovarian (A2780) tumor xenograft model, we examined the effect of Mg status on cisplatin-induced AKI and the anti-tumor efficacy of cisplatin. In both non-tumor- and tumor-bearing mice, Mg deficiency (MgD) significantly worsened cisplatin-induced AKI (based on BUN, inflammation, apoptosis and histological scores), while MgS significantly protected against cisplatin-induced AKI. Tumor growth was inhibited by cisplatin and further inhibited by MgS on day22. MgD did not affect tumor growth or cisplatin-mediating tumor killing. Ongoing studies are exploring the role of Mg status in tumor growth and cisplatin-induced AKI in additional tumor models in mice. In summary, MgD worsens and MgS protects against cisplatin-induced AKI, as evidenced by improved kidney function, and reduced renal inflammation and apoptosis. While improving kidney function, MgS also improved cisplatin-induced tumor killing. Mechanistic studies reveal that MgD increases accumulation through regulating cisplatin transporter expression/function in the kidneys; these effects are not observed in the tumor. These findings warrant future large scale studies to assess Mg status and aggressive Mg replacement therapy in cisplatin-treated patients. In addition, assessment of dose, formulation, and timing/duration of Mg replacement in cisplatin-treated patients should be considered to promote renoprotection.