Document Type

Article

Publication Date

5-4-2021

Identifier

DOI: 10.1016/j.ekir.2021.04.023; PMCID: PMC8258499

Abstract

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.

Journal Title

Kidney Int Rep

Volume

6

Issue

7

First Page

1775

Last Page

1787

Keywords

Nrf2; chronic inflammation; chronic kidney disease; mitochondrial dysfunction; oxidative stress; resident kidney cells

Comments

This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://www.kireports.org/article/S2468-0249(21)01136-0/fulltext

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Nephrology Commons

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