A comparative review of murine models of repeated low-dose cisplatin-induced chronic kidney disease

Abstract

This Review evaluates various mouse and rat models of chronic kidney disease (CKD) that result from repeated low-dose cisplatin (RLDC) treatment while also discussing ethical considerations on the topic. Cisplatin can cause nephrotoxicity, and high doses of cisplatin can cause acute kidney injury. The RLDC regimen has been used in the treatment of solid organ cancers and has shown efficacy in reducing the occurrence of acute kidney injury in patients. However, prolonged treatments may lead to CKD. Mouse and rat models that effectively replicate the pathological features of CKD are invaluable for studying the mechanisms of the disease and exploring potential therapeutic interventions. Whereas administration of a single higher dose in some RLDC models may lead to higher mortality rates, a single lower dose may not replicate the fibrotic characteristics of CKD. Here we gathered information on mouse and rat models of RLDC-induced CKD and analyzed the impact of different variables, such as animal age, cisplatin dosage and administration frequency, on success rates, mortality rate and weight loss. Among the different models, weekly intraperitoneal administration of 8 mg/kg or 9 mg/kg of cisplatin for a total of 4 weeks in 12-week-old male C57BL/6 mice showed the most similar clinical characteristics of CKD while adhering to ethical requirements. In this Review, we suggest the best timings for both drug intervention and observation based on the biological traits of the model. Furthermore, given the limited research available on RLDC-induced CKD rat models, it is urgent to focus on developing RLDC methods that can induce detailed characteristics of CKD in rats. This Review assesses murine models of chronic kidney disease caused by low-dose cisplatin treatment, discussing ethical considerations as well as variables’ impact on success, mortality and weight loss. The authors also suggest optimal intervention timings.