Acute kidney injury and maladaptive tubular repair leading to renal fibrosis.
Acute kidney injury and maladaptive tubular repair leading to renal fibrosis.
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DOI：
10.1097/mnh.0000000000000605
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发表时间：
2020-03
影响因子：
3.2
通讯作者：
Samuel Mon-Wei Yu;J. Bonventre
中科院分区：
文献类型：
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作者：
Samuel Mon-Wei Yu;J. Bonventre
综述目的尽管急性肾损伤（阿基）检测有所改善，但阻止阿基进展为慢性肾病（CKD）的治疗选择仍然有限。在这篇综述中，我们重点关注与阿基到CKD连续体的病理生理学相关的最新发现，特别是涉及肾小管上皮细胞，并讨论相关的正在进行的临床试验。虽然我们的重点是损伤的肾小管上皮细胞作为级联事件的引发者，导致对肾脏其他细胞的旁分泌效应，但来自各种肾脏细胞类型的适应不良反应的总和最终导致CKD的纤维化和功能障碍特征。我们将重点关注的最新发现包括但不限于以下特征：肾小管上皮细胞中细胞周期停滞和细胞衰老之间的关联及其对肾纤维化、慢性炎症伴持续细胞因子产生和未修复肾小管中淋巴细胞浸润、线粒体功能障碍和胞质线粒体DNA在纤维形成中的独特作用的贡献，脯氨酰羟化酶结构域蛋白作为潜在的治疗靶点，以及涉及Hippo/yes相关蛋白/转录辅激活因子与PDZ结合途径的新机制。总结：通过更好地了解纤维化途径，将为解决CKD进展的潜在治疗选择提供信息。最近的进展表明在导致纤维化的各种途径中有其他药物靶点。
PURPOSE OF REVIEW Despite improvements in acute kidney injury (AKI) detection, therapeutic options to halt the progression of AKI to chronic kidney disease (CKD) remain limited. In this review, we focus on recent discoveries related to the pathophysiology of the AKI to CKD continuum, particularly involving the renal tubular epithelial cells, and also discuss related ongoing clinical trials. While our focus is on injured renal tubular epithelial cells as initiators of the cascade of events resulting in paracrine effects on other cells of the kidney, the summation of maladaptive responses from various kidney cell types ultimately leads to fibrosis and dysfunction characteristic of CKD. RECENT FINDINGS Recent findings that we will focus on include, but are not limited to, characterizations of: the association between cell cycle arrest and cellular senescence in renal tubular epithelial cells and its contribution to renal fibrosis, chronic inflammation with persistent cytokine production and lymphocyte infiltration among unrepaired renal tubules, mitochondrial dysfunction and a unique role of cytosolic mitochondria DNA in fibrogenesis, prolyl hydroxylase domain proteins as potential therapeutic targets, and novel mechanisms involving the Hippo/yes-associated protein/transcriptional coactivator with PDZ-binding pathway. SUMMARY Potential therapeutic options to address CKD progression will be informed by a better understanding of fibrogenic pathways. Recent advances suggest additional drug targets in the various pathways leading to fibrosis.