Animal Models for Acute Kidney Injury

Acute kidney injury (AKI) is classified into three types according to its pathophysiology: prerenal, intrinsic renal, and post-renal AKI. Experimental models of AKI can be divided into two categories: in vivo and in vitro. Models can be further subdivided according to how AKI is simulated. The pathophysiology of intrinsic renal and post-renal AKI has been investigated using animal models. Most studies have been conducted in murine models using male mice or rats, while large mammals like sheep, pigs, and monkeys have been used in a limited number of studies. The intrinsic renal AKI model is divided into septic vs. aseptic AKI. Aseptic AKI is subdivided into ischemic vs. nephrotoxic AKI. Lipopolysaccharides (LPS) injection or cecal ligation and puncture (CLP) have been used to simulate the septic AKI model in rodents. Ischemic AKI is the most extensively investigated field to date because ischemic AKI is the most common and serious cause of AKI in both native kidneys and renal allografts. Ischemia-reperfusion injury (IRI) surgery has been used to induce ischemic AKI. There are two different methods of IRI surgery: laparotomy vs. flank approach. Warm temperature and male sex are critical to induction of sufficient grade of renal injury in this model. Many nephrotoxicants pertinent to human disease have been used to reproduce nephrotoxic AKI in rodent models. Cisplatin, a common chemotherapeutic agent, has many pathophysiologic features that overlap with IRI. Other nephrotoxicants such as gentamicin or glycerol were studied in the past, whereas much more attention has recently been devoted to environmental nephrotoxicants such as cadmium. However, variant susceptibility to different doses of nephrotoxicants is a big hurdle to set up a reproducible and consistent model of nephrotoxic AKI. Post-renal AKI is simulated with ureteral obstruction surgery, whereas the unilateral ureteral obstruction (UUO) model has frequently been used. Although some novel findings have been reported through numerous studies using murine AKI models, AKI still remains a challenging condition that lacks specific diagnostic or therapeutic tools because of species barriers or experimental settings. Animal AKI models using mammals genetically closer to human like monkeys would be valuable to simulate human AKI more appropriately.