Elucidation of the mechanism in cisplatin-induced renal failure anddevelopment of drug therapy aimed at the mitigation of the renal toxicity of cisplatin.

顺铂是一种具有很强的抗肿瘤作用的化疗药物。然而，在某些情况下，顺铂经常因肾毒性而停用。因此，我们试图阐明顺铂肾毒性的作用机制，寻找改善顺铂肾毒性的治疗方法，从而在不干扰顺铂抗癌作用的前提下，降低顺铂的肾毒性，从而阐明顺铂肾毒性的作用机制。在本研究中，我们提出了顺铂导致肾功能衰竭的一种新机制(S)，即顺铂加速依赖于糜酶的IL-18的产生，从而刺激醛固酮的合成，顺铂的过度排泄导致肾脏炎症。因此，联合应用糜酶活性抑制剂(S)或与其受体结合的醛固酮与顺铂可减轻顺铂所致肾损害的发病机制。

Cisplatin is a chemotherapeutic agent having a potent anti-tumor effect. However, in some cases, cisplatin has often withdrawn due to renal toxicity. Therefore, we tried to elucidate mechanisms involved in renal toxicity of cisplatin, and find out therapy to improve it, and thus, it might be able to reduce the nephrotoxicity without disturbing the anticancer effect of cisplatin by combination with drugs to elucidate mechanisms involved in renal toxicity of cisplatin. In the present research, we have proposed a novel mechanism(s) on the development of cisplatin-induced renal failure that cisplatin accelerates chymase-dependent production of IL-18 which stimulates aldosterone synthesis, and that extended excretion of cisplatin causes renal inflammation. Thus, concomitant use of inhibitor(s) of chymase activity or aldosteron binding to its receptor with cisplatin could be reducing the pathogenesis of renal damage by cisplatin therapy.