Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.
Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.
复制标题
缺血再灌注诱导的急性肾损伤小鼠模型的长期结果。
DOI：
10.1152/ajprenal.00305.2019
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
deCaestecker,MarkP
中科院分区：
文献类型：
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作者：
Scarfe,Lauren;Menshikh,Anna;Newton,Emily;Zhu,Yuantee;Delgado,Rachel;Finney,Charlene;deCaestecker,MarkP
严重急性肾损伤具有高死亡率，并且是进行性慢性肾脏疾病的危险因素。在临床前研究中确定的潜在疗法中，没有一种成功改善了临床结局。这种失败的部分原因是动物模型很少反映人类疾病的复杂性：大多数临床前研究都是短期的，通常在健康的年轻雄性小鼠中进行。在临床前模型中有效的治疗方法更有可能预测临床成功，这些模型具有急性肾损伤患者的常见临床特征，包括遗传多样性，不同性别和合并症，并评估长期结局。在这里，我们通过监测长期功能和组织学对损伤的反应，评估了延迟肾切除术后缺血再灌注损伤对慢性肾脏疾病的易感性。我们定义了诱导长期损伤后肾功能不全和纤维化而不增加死亡率的条件，并评估了小鼠品系、性别和预先存在的糖尿病对这些反应的影响。
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.