Sharp Cierra N, Siskind Leah J
Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; and.
Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky; and
Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F835-F841. doi: 10.1152/ajprenal.00285.2017. Epub 2017 Jul 19.
Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury.
顺铂是一种用于治疗多种癌症的强效化疗药物。然而,其剂量限制性副作用是肾毒性,可导致急性肾损伤(AKI)。发生急性肾损伤的患者死亡风险增加,并且更有可能发展为慢性肾脏病(CKD)。不幸的是,目前尚无针对急性肾损伤的治疗干预措施。有人认为,缺乏治疗方法部分是由于用于研究顺铂诱导的急性肾损伤的既定小鼠模型无法重现患者接受的顺铂给药方案。近年来,人们致力于开发更具临床相关性的顺铂诱导的肾损伤模型,许多工作集中在在数周内给予多次低剂量顺铂。这些模型可用于重现急性肾损伤后慢性肾脏病的发展过程,从而增加识别顺铂诱导的肾损伤新治疗靶点的可能性。