a Laboratory of Cellular and Molecular Biology , Center for Cancer Research, National Cancer Institute , Bethesda , MD , USA.
b IRTOMIT , Inserm U1082 , Poitiers , France.
Expert Opin Ther Targets. 2019 Jun;23(6):495-509. doi: 10.1080/14728222.2019.1609451. Epub 2019 May 3.
Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs. Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers. Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ. Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes. An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.
肾缺血再灌注损伤（IRI）是临床医生在围手术期和重症监护等多种临床环境中面临的重大临床挑战。肾 IRI 引起的急性肾损伤（AKI）是一个全球性的公共卫生问题，与高发病率、死亡率和医疗保健成本有关。
本文重点介绍与移植相关 AKI 的病理生理学，以及细胞应激反应在以下三个方面交叉点的最新发现：1. 未折叠蛋白反应；2. 线粒体功能障碍；3. 盐皮质激素受体拮抗剂的益处。最后，为读者提供了一些观点。
肾 IRI 是由器官血流突然和暂时受损引起的。确定 IRI 中涉及的潜在细胞级联反应将有助于我们识别新的干预靶点，以减轻 IRI，从而有可能改善移植结果。与靶向下游炎症和纤维化过程相比，靶向细胞损伤上游的线粒体功能和细胞生物能量可能具有几个优势。对导致肾损伤的细胞病理生理机制的深入了解，有望为未来预防和治疗损伤提供更好的靶向治疗。
