Modeling Cisplatin-Induced Kidney Injury to Increase Translational Potential.
Modeling Cisplatin-Induced Kidney Injury to Increase Translational Potential.
复制标题
模拟顺铂引起的肾损伤以增加转化潜力。
作者：
Sears,SophiaM;Orwick,Andrew;Siskind,LeahJ
背景顺铂引起的肾损伤是阻碍癌症患者治疗的主要挑战。30%的顺铂治疗患者发生急性肾损伤（阿基）。即使没有发生阿基的患者也有长期肾功能下降和慢性肾脏疾病发展的风险。尽管研究人员尽了最大的努力，没有治疗剂来治疗或预防顺铂诱导的肾损伤已经使其通过2期临床试验。SummaryModeling顺铂诱导的肾损伤在啮齿动物中主要是使用一个单一的，高剂量的损伤模型。较新的损伤模型已经利用重复、低或中等剂量的顺铂来纳入肾损伤后适应不良修复过程的研究。我们认为，利用所有这些模型是重要的，以了解和治疗不同类型的顺铂诱导的肾损伤患者在临床上发展。阐明合并症，如癌症和大型动物模型的发展也是至关重要的，以增加人类的相关性，我们的studies.Key MessagesUtilizing顺铂诱导的肾损伤，包括相关的合并症和生物学变量，和大型动物模型的发展多剂量模型将增加临床前研究的转化潜力。
BackgroundCisplatin-induced kidney injury is a major challenge hindering treatment of cancer patients. Thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Even patients that do not develop AKI are at risk for long-term decline in renal function and development of chronic kidney disease. Despite researchers’ best efforts, no therapeutic agents to treat or prevent cisplatin-induced kidney injury have made it past phase 2 clinical trials.SummaryModeling cisplatin-induced kidney injury in rodents has primarily been done using a single, high-dose model of injury. Newer models of injury have utilized repeated, low, or intermediate doses of cisplatin to incorporate the study of maladaptive repair processes following a renal insult. We believe that utilization of all these models is important to understand and treat the diverse types of cisplatin-induced kidney injury patients develop in the clinic. Incorporating comorbidities such as cancer and development of large animal models is also vital to increasing the human relevance of our studies.Key MessagesUtilizing multiple dosing models of cisplatin-induced kidney injury, including relevant comorbidities and biological variables, and development of large animal models will increase the translational potential of preclinical studies.