Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2

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-kB-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 wellelucidated, 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.

Cadmium-Induced Kidney Injury in Mice Is Counteracted by a Flavonoid-Rich Extract of Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, via the Enhancement of Different Defense Mechanisms

“…In the last decade, several studies suggested that disruption of the Nrf2 signaling pathway was involved in several kidney diseases [ 74 , 75 , 76 ]. Nrf2 is a crucial transcription factor that plays a pivotal role in inducing the expression of cellular defense enzymes to counteract oxidative stress.…”

Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome

“…Oxidative stress is a key component of several age-related pathologies, including CVDs and acute CKD, and the role of different pro-oxidant molecules, as well as the therapeutic effects of several antioxidants, have been widely studied both in experimental models and in clinical trials [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ].…”

Molecular Mechanistic Pathways Targeted by Natural Antioxidants in the Prevention and Treatment of Chronic Kidney Disease

“…The reduced levels of AMPK contribute to an increase in Keap-1-Nrf-2 complex and a reduction in binding of Nrf-2 to the antioxidant response element and transcription of antioxidant enzymes, including heme oxygenase-1 (HO-1), super oxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [ 46 ]. In addition, the inflammatory milieu related to CKD leads to reduced Nrf-2 transcriptional activity and renal antioxidant capacity [ 47 ].…”