Cancer therapy and renal injury

Cisplatin and other platinum derivatives are among the most effective chemotherapeutic agents against solid tumors including ovarian, head and neck carcinomas, and germ cell tumors. The major side effect of cisplatin is nephrotoxicity. While several antineoplastic agents frequently exhibit nephrotoxicity, the platinum derivatives are among the most frequent compounds leading to renal injury (1). There also can be synergistic nephrotoxic effects of cisplatin with other chemotherapeutic agents such as the taxol compounds (2). Moreover, in hematopoietic cell transplantation (HCT), there ap-pears to be a dramatic interaction between chemotherapeutic agents, such as cisplatin, and immunosuppressive agents such as cyclosporine. Specifically, nephrotoxicity, as assessed by a 25% loss of glomerular filtration rate (GFR), has been observed in 56% of autologous HCTs, in which immunosuppressive therapy is not used, but in more than 90% of allogeneic HCT, which requires immunosuppression (3, 4). Moreover, mortality is 7% in autologous HCTs in which cisplatin and other antineoplastic drugs are used without immunosuppression. In contrast, the mortality rises to 58% in allogeneic HCTs when the antineoplastic drugs are combined with immunosuppressive drugs, particularly calcineurin inhibitors, such as cyclosporine.