Modeling Cisplatin-Induced Kidney Injury to Increase Translational Potential

Abstract

Background: Cisplatin-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. Summary: Modeling 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 Messages: Utilizing 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.