Could Low-Protein Diet Modulate Nrf2 Pathway in Chronic Kidney Disease?

Abstract

Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly linked to clinical outcomes such as protein energy wasting and cardiovascular disease. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is the master regulator of antioxidant genes, regulating the expression of detoxifying enzymes of phase II and antioxidant responses. Furthermore, Nrf2 can also regulate anti-inflammatory cellular responses, by inhibiting nuclear factor kappa B activity (transcription factor that promotes inflammation). Therefore, modulating Nrf2 can be a new therapeutic approach to reduce inflammation and oxidative stress in CKD. Low-protein diet (LPD) prescribed for nondialysis CKD patients presents numerous benefits already well established, including reduction of inflammation and oxidative stress. However, there is no available data regarding the relationship between LPD and Nrf2 modulation in these patients. This review aims to discuss the impact, if any, of LPD on Nrf2 expression, in nondialysis CKD patients.

Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria

“…Nrf‐1 transcription is regulated also by PPAR‐β in muscle of exercised rats, a mechanism that increases MB through upregulation of AMP‐activated protein kinase (AMPK) and Nrf‐1/Nrf‐2 that integrate their effects on the nuclear genes of MB with promotion of the replication and transcription of TFAM. The latter is a multifunctional protein that belongs to the high‐mobility group (HMG) proteins that are characterized by their ability to bend, wrap and unwind mtDNA without sequence specificity, but with preferential interaction with some identified regions …”

“…The latter is a multifunctional protein that belongs to the high-mobility group (HMG) proteins that are characterized by their ability to bend, wrap and unwind mtDNA without sequence specificity, but with preferential interaction with some identified regions. 18,[21][22][23] Tumour suppressor protein p53 is known as the "guardian of the mitochondria genome" 24 and has the ability to modulate expression of both the mitochondrial and the nucleus genes. 25,26 Metabolic stress results in p53 activation by its key modulator PGC-1α and triggers cell-cycle arrest, reactive oxygen species (ROS) clearance or apoptosis.…”

Nrf2 in early vascular ageing: Calcification, senescence and therapy

“…Participants showed decreased inflammatory markers and an improved lipid profile via Nrf2 regulation of vitagene and heat shock proteins (Hsp) proteins [151,154]. These data support growing evidence for the impact of nutrition on Nrf2-Keap1 signaling pathway [151,[155][156][157]. Since high salt-loading down-regulates Nrf2 expression in kidney collecting duct cells [158] this suggest that high salt diets should be avoided.…”

“…This has been demonstrated by the restriction of protein in the diet of CKD patients. A low protein diet reduce levels of oxidative stress and inflammation via the modulation of Nrf2 expression in non-dialysis CKD patients [156,160,167], and has been hypothesized to modulate the gut microbiota and reduce the generation of uremic toxins, such as PCS and IS [160]. The source of protein within the diet has also been shown to be significant, with plant protein intake being associated with lower production of uremic toxins and lower serum phosphorus and warrants further exploration, [168,169].…”

Effects of calcium and magnesium-balanced deep sea water on antioxidation in kidney cells

“…Catalase (CAT) activity was highest in the NaCl group and conversely lower in the HM and HMHC groups, than in the CON group. The protective effect of magnesium against oxidative stress gave rise to the apparently reduced CAT activity in HM and HMHC groups, compared to the other groups 산화효소와 관련된 유전자를 활성화한다 [27].…”