Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread

Abstract

Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products—AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.

Cocoa ameliorates renal injury in Zucker diabetic fatty rats by preventing oxidative stress, apoptosis and inactivation of autophagy

“…), which leads to the activation of different routes, such as nuclear factor-κB, MAPKs, etc. 40 Therefore, the involvement of different signals related to oxidative stress on the cocoa-induced protective effect cannot be ruled out. Excessive oxidative stress results in the activation of different pathways, including MAPKs.…”

NAFLD as a driver of chronic kidney disease

“…107 As mentioned, dyslipidaemia is a key feature of MetS, NAFLD and CKD and the specific dyslipidaemia involves an increase in hepatic-derived triglyceriderich lipoproteins. Oxidative stress is a key feature of NAFLD [108][109][110] and CKD; [111][112][113] both oxidative stress and an increase in triglyceride-rich lipoproteins (such as very low-density lipoprotein and remnant lipoproteins) are key regulators of platelet activation. [114][115][116][117] With oxidative stress and kidney dysfunction, there is a reduction in anti-oxidant protective factors produced by the kidneys, such as the Klotho protein, 118 and generation of metabolites such as plasma F2-isoprostanes, 8-oxo-7,8dihydro-2'-deoxyguanosine, malonyldialdehyde, advanced oxidation protein products, carbamylated proteins, asymmetric dimethylarginine and oxidised lipoprotein particles.…”

Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy

“…Both mechanisms have adverse synergistic effects [ 40 ]. Oxidative stress is directly linked to podocyte damage, proteinuria, and tubulointerstitial fibrosis [ 43 ]. Additionally, vascular oxidative stress has an important role in CKD progression ( Figure 1 ) [ 43 , 44 , 45 , 46 ].…”