Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.

Scarfe L, Menshikh A, Newton E, Zhu Y, Delgado R, Finney C, de Caestecker MP
Am J Physiol Renal Physiol. 2019 317 (4): F1068-F1080

PMID: 31411074 · PMCID: PMC7132317 · DOI:10.1152/ajprenal.00305.2019

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.

MeSH Terms (17)

Acute Kidney Injury Animals Diabetes Mellitus, Experimental Diabetic Nephropathies Disease Models, Animal Female Fibrosis Kidney Function Tests Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Nephrectomy Reperfusion Injury Sex Characteristics Species Specificity

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