Tubular atrophy in the pathogenesis of chronic kidney disease progression.
Tubular atrophy in the pathogenesis of chronic kidney disease progression.
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DOI：
10.1007/s00467-015-3169-4
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Schelling JR
中科院分区：
文献类型：
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作者：
Schelling JR
长期以来，慢性肾脏疾病（CKD）研究的重点一直放在肾小球上，这是合理的，因为肾小球滤过发生在肾小球，而且很大一部分进行性CKD与显著的肾小球病理相关。然而，几十年来，人们已经知道小管萎缩也是CKD的一个标志，并且作为CKD中GFR下降的预测因子优于肾小球病理。然而，调查小管萎缩原因的研究少得多，确定潜在治疗靶点的研究更少。本文旨在探讨小管萎缩的可能机制，包括小管上皮细胞凋亡、细胞衰老、小管周围毛细血管稀疏和下游小管缺血、氧化应激、小管肾小球、上皮-间质转化、间质炎症、脂肪毒性和Na+/H+交换物-1 （NHE1）失活。在对肾小管萎缩（和间质纤维化）病理生理学有了更好的了解后，就有可能考虑肾小球和肾小管串联治疗策略，其方式类似于癌症化疗方案，即使用多种药物同时靶向不同的机制途径。
The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD, and is superior to glomerular pathology as a predictor of GFR decline in CKD. Nevertheless there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na+/H+ exchanger-1 (NHE1) inactivation. Upon obtaining a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.