Animal models of sepsis and sepsis-induced kidney injury

Abstract

Sepsis is characterized by a severe inflammatory response to infection, and its complications, including acute kidney injury, can be fatal. Animal models that correctly mimic human disease are extremely valuable because they hasten the development of clinically useful therapeutics. Too often, however, animal models do not properly mimic human disease. In this Review, we outline a bedside-to-bench-to-bedside approach that has resulted in improved animal models for the study of sepsis - a complex disease for which preventive and therapeutic strategies are unfortunately lacking. We also highlight a few of the promising avenues for therapeutic advances and biomarkers for sepsis and sepsis-induced acute kidney injury. Finally, we review how the study of drug targets and biomarkers are affected by and in turn have influenced these evolving animal models.

Figure 1. Simplified clinical course of sepsis.

Progression of disease is complex, nonlinear, and varies from one patient to another. Shown is an outline of selected landmark events and processes that appear to be common among patients and some animal models. DIC, disseminated intravascular coagulation.

Figure 2. Histology of AKI in a clinically relevant model of CLP-induced sepsis.

Periodic acid–Schiff (PAS) staining of mouse kidney cortex 24 hours after CLP surgery (A) or sham surgery (B). Pink staining of brush border is visible in sham cortical tubules, and loss of brush border is evident, as is mild dilation, after CLP. Vacuolization is seen after CLP in almost all tubules, most prominently in two tubules in the upper-right corner (circled). Original magnification, ×400. Scale bar: 200 μm. Reproduced from the American Journal of Physiology: Renal Physiology (63).