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慢性肾脏病中的肾脏脂质代谢紊乱和脂滴积累。

Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease.

机构信息

Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA.

Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL, USA.

出版信息

Nat Rev Nephrol. 2023 Oct;19(10):629-645. doi: 10.1038/s41581-023-00741-w. Epub 2023 Jul 27.

Abstract

Chronic kidney disease (CKD) is a global health problem with rising incidence and prevalence. Among several pathogenetic mechanisms responsible for disease progression, lipid accumulation in the kidney parenchyma might drive inflammation and fibrosis, as has been described in fatty liver diseases. Lipids and their metabolites have several important structural and functional roles, as they are constituents of cell and organelle membranes, serve as signalling molecules and are used for energy production. However, although lipids can be stored in lipid droplets to maintain lipid homeostasis, lipid accumulation can become pathogenic. Understanding the mechanisms linking kidney parenchymal lipid accumulation to CKD of metabolic or non-metabolic origin is challenging, owing to the tremendous variety of lipid species and their functional diversity across different parenchymal cells. Nonetheless, multiple research reports have begun to emphasize the effect of dysregulated kidney lipid metabolism in CKD progression. For example, altered cholesterol and fatty acid metabolism contribute to glomerular and tubular cell injury. Newly developed lipid-targeting agents are being tested in clinical trials in CKD, raising expectations for further therapeutic development in this field.

摘要

慢性肾脏病(CKD)是一个全球性的健康问题,其发病率和患病率呈上升趋势。在导致疾病进展的几种发病机制中,肾脏实质中脂质的积累可能会引发炎症和纤维化,正如在脂肪肝疾病中所描述的那样。脂质及其代谢物具有几个重要的结构和功能作用,因为它们是细胞膜和细胞器的组成部分,作为信号分子,并用于能量产生。然而,尽管脂质可以储存在脂滴中以维持脂质平衡,但脂质的积累也可能会导致疾病。由于脂质种类繁多,不同实质细胞中的功能多样性,理解将肾脏实质脂质积累与代谢或非代谢来源的 CKD 联系起来的机制具有挑战性。尽管如此,多项研究报告已经开始强调肾脏脂质代谢失调在 CKD 进展中的作用。例如,胆固醇和脂肪酸代谢的改变会导致肾小球和肾小管细胞损伤。新开发的脂质靶向药物正在 CKD 的临床试验中进行测试,这为该领域的进一步治疗发展带来了期望。

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