The morbidity and mortality of acute kidney injury (AKI)—especially sepsis AKI—have remained high, despite numerous attempts at novel therapies. Many agents have worked in animals but failed in clinical trials. Effective treatment likely requires early detection and a better understanding of the pathophysiology of human AKI. Our long-term goals are to find markers to detect AKI and to develop therapies to treat and prevent AKI. We are developing better models that more closely mimic sepsis and sepsis AKI.
Clinically relevant sepsis model of AKI:
Sepsis is one of the leading causes of AKI, and 50 percent of patients with sepsis develop AKI. The pathogenesis of sepsis-induced AKI is very poorly understood. There are no drugs to treat sepsis-induced AKI, in part because of the lack of animal models that mimic the human disease. Therefore, we developed several new mouse models based on the cecal ligation and puncture model of polymicrobial sepsis, which has hyperdynamic and hypodynamic phases typical of human sepsis. To make the model realistic, we gave the animals pre-existing conditions (elderly animals or those with chronic kindey disease), and treated the animals with postoperative fluids and antibiotics. The mice developed biochemical and histological renal injury that was similar to human AKI. We are characterizing this model and using it to test treatment strategies.