**6. Sepsis and sepsis-associated AKI**

#### **6.1 Background**

Sepsis is characterized by a severe inflammatory response to infection, and one of its complications is acute kidney injury. Animal models that mimic the pathophysiology of human sepsis and associated acute kidney injury are valuable because they aid in identifying molecular targets and in developing therapeutics. Too often, animal models do not properly mimic human disease. In this chapter, we describe the three commonly used approaches that have resulted in improved animal models to study sepsis.

Sepsis is a complex condition that results in a dysregulated host response to an infection and is associated with unacceptably high mortality [38]. Sepsis-associated acute kidney injury (S-AKI) is a common end organ manifestation in hospitalized and critically ill patients and is associated with high mortality and increased risk of developing chronic comorbidities [39, 40]. As individual syndromes, sepsis and AKI render the host susceptible to each other. Sepsis has a complex and unique pathophysiology, which makes S-AKI a distinct syndrome from any other phenotype of AKI. Identifying the exact onset of AKI in sepsis is nearly impossible, leading to difficulty in timely intervention for prevention of renal injury. This has limited our understanding of pathophysiologic mechanisms and precluded the development of effective therapies. The pathogenesis of S-AKI is multifactorial and involves systemic cytokine storm, hypoxia, mitochondrial dysfunction, tubular epithelial cell injury, and endothelial dysfunction [41, 42].

Local mechanisms cannot be identified and studied in humans, and hence the use of relevant animal models is paramount to eventually identify new therapeutic target to treat a syndrome still mainly managed by antibiotics and fluid resuscitations. Animal models of sepsis need to reproduce the complexity and severity of human sepsis, mimic the key hemodynamic and immunologic (proinflammatory stimulation, anti-inflammatory counter regulation, i.e., immune depression) stages as well as the modest histological findings. The sepsis inducing procedure should result in toxicity and bacteremia and should result as metabolic and physiologic

## *Mouse Models of Acute Kidney Injury DOI: http://dx.doi.org/10.5772/intechopen.97523*

changes. Furthermore, the septic insult should manifest over sufficient length of time to allow the study of its evolution and finally the model should be reproducible and inexpensive.

Below we discuss the three commonly used animal models of sepsis and S-AKI and summarize the advantage and shortcomings of each.
