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ABSTRACT

Cisplatin, a commonly used cancer chemotherapeutic, has a dose limiting side effect of nephrotoxicity. According to the Risk, Injury, Failure, Loss of Function, and End Stage Renal Disease (RIFLE) criteria of kidney injury, approximately 30% of patients administered cisplatin suffer from kidney injury and there is currently no treatment for cisplatin‐induced kidney injury other than palliative care. Suramin, FDA‐approved for the treatment of trypanosomiasis, improves kidney function following various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin‐induced kidney injury. Suramin treatment prior to cisplatin administration reduced cisplatin‐induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin‐induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 hours after cisplatin improved kidney function, suggesting that the mechanism of protection is neither via inhibiting tubular cisplatin uptake nor its metabolism to nephrotoxic species. If suramin is to be utilized in the context of cancer, then suramin cannot prevent cisplatin‐induced cytotoxicity within tumors. Mice harboring lung adenocarcinomas were pretreated with suramin and then administered cisplatin. Lung histology and markers of kidney function indicated that suramin protected mice from cisplatin‐induced acute kidney injury, but did not inhibit cisplatin induced cytotoxic effects within the tumor. These results provide evidence that suramin has great potential as a renoprotective agent for the treatment/prevention of cisplatin‐induced acute kidney injury.

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