Stenvinkel Peter, Chertow Glenn M, Devarajan Prasad, Levin Adeera, Andreoli Sharon P, Bangalore Sripal, Warady Bradley A
Department of Renal Medicine M99, Karolinska University Hospital at Huddinge, Karolinska Institutet, Stockholm, Sweden.
Division of Nephrology, Stanford University, Stanford, California, USA.
Kidney Int Rep. 2021 May 4;6(7):1775-1787. doi: 10.1016/j.ekir.2021.04.023. eCollection 2021 Jul.
Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB- and nuclear factor, erythroid 2 like 2 (Nrf2)-mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2.
尽管近年来慢性肾脏病（CKD）的管理取得了进展，但这些患者的发病率和死亡率仍然很高。虽然压力介导的损伤是CKD疾病进展的一种公认机制，但新出现的数据表明，涉及慢性炎症、氧化应激、缺氧、衰老和线粒体功能障碍的中间表型在CKD的病因、进展和病理生理学中起关键作用。多种因素促进CKD中的慢性炎症，包括氧化应激和肾固有细胞采用促炎表型。分别通过NF-κB和核因子红细胞2样2（Nrf2）介导的基因转录来调节促炎和抗炎因子，在肾小球和肾小管细胞对肾损伤的反应中起关键作用。慢性炎症导致CKD中肾小球滤过率（GFR）下降。虽然慢性炎症在糖尿病肾病（DKD）中的作用已得到充分阐明，但现在有大量证据表明，在其他几种疾病中，如Alport综合征、常染色体显性多囊肾病（ADPKD）、IgA肾病（IgAN）和局灶节段性肾小球硬化（FSGS），未解决的炎症过程会导致纤维化和最终的终末期肾病（ESKD）。在这篇综述中，我们旨在阐明慢性炎症在各种肾脏疾病的病理生理学和疾病进展中的机制，重点是Nrf2。
