Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.
Lauren N LopezAnna MenshikhEmily NewtonYuantee ZhuRachel DelgadoCharlene FinneyMark P de CaesteckerPublished in: American journal of physiology. Renal physiology (2019)
Severe acute kidney injury has a high mortality and is a risk factor for progressive chronic kidney disease. None of the potential therapies that have been identified in preclinical studies have successfully improved clinical outcomes. This failure is partly because animal models rarely reflect the complexity of human disease: most preclinical studies are short term and are commonly performed in healthy, young, male mice. Therapies that are effective in preclinical models that share common clinical features seen in patients with acute kidney injury, including genetic diversity, different sexes, and comorbidities, and evaluate long-term outcomes are more likely to predict success in the clinic. Here, we evaluated susceptibility to chronic kidney disease after ischemia-reperfusion injury with delayed nephrectomy by monitoring long-term functional and histological responses to injury. We defined conditions required to induce long-term postinjury renal dysfunction and fibrosis without increased mortality in a reproducible way and evaluate effect of mouse strains, sexes, and preexisting diabetes on these responses.
Keyphrases
- acute kidney injury
- chronic kidney disease
- genetic diversity
- cardiac surgery
- end stage renal disease
- ischemia reperfusion injury
- cell therapy
- endothelial cells
- cardiovascular events
- oxidative stress
- mouse model
- type diabetes
- case control
- cardiovascular disease
- escherichia coli
- high glucose
- multiple sclerosis
- risk factors
- primary care
- drug induced
- diabetic rats
- robot assisted
- adipose tissue
- skeletal muscle
- metabolic syndrome