Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease

Abstract

Patients with moderate to advanced chronic kidney disease or end-stage renal disease have a greatly increased cardiovascular risk that cannot be explained entirely by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation have been proposed as nontraditional cardiovascular risk factors in this patient population. Oxidative stress reflects the redox balance between oxidant generation and antioxidant mechanisms. The generation of reactive oxygen species is not simply a random process that oxidizes nearby macromolecules, but, in many instances, the oxidants target particular amino acid residues or lipid moieties. Oxidant mechanisms are now recognized to be intimately involved in cell signaling and to be vital components of the immune response. This is equally true for antioxidant mechanisms as well. In the progression of chronic kidney disease, the redox balance is not in equilibrium and is tipped toward oxidation, resulting in the dysregulation of cellular process and subsequent tissue injury. In this review we discuss the major oxidant and antioxidant pathways and the biomarkers to assess redox status. We also review the data linking the pathogenesis of oxidative stress, inflammation, and the progressive loss of kidney function in chronic kidney disease.

Cysteamine Modulates Oxidative Stress and Blocks Myofibroblast Activity in CKD

“…There is a substantial body of evidence supporting the hypothesis that increased oxidative stress plays an important role in the development of fibrotic diseases in humans. 5,32,33 Prior studies centered on the reduction of oxidized macromolecules as the critical component to limiting disease progression, 34,35 rather than the specific redoxsensitive pathways or target cells that are directly modulated by antioxidants. 36,37 We found that cysteamine bitartrate treatment resulted in a substantial reduction in protein oxidation (.50%) despite no change in total thiol levels at advanced time points.…”

“…Thiol groups react with almost all physiologic oxidants and can reduce them before they trigger harmful reactions. 5 Chronic kidney injury depletes endogenous intracellular and extracellular antioxidant systems, resulting in increased tissue oxidative stress. [6][7][8] Cysteamine bitartrate is a simple yet interesting aminothiol that is approved by the US Food and Drug Administration for the treatment of patients with cystinosis.…”

Association Between Clinical Risk Factors and Progression of Chronic Kidney Disease in Children

“…Moreover, the available data are limited to information that is routinely collected in the database at 6-months intervals, not allowing for more complete or detailed information. Most importantly, it did not allow for the assessment of an association between chronic inflammatory state or degree of proteinuria and risk of disease progression, both areas of significant interest of late (19).…”

Effect of pentoxifylline and 5-fluorouracil/triamcinolone on laryngotracheal stenosis developing as a complication of tracheostomy: study in rats

“…Oxidative stress plays an important role in the development of fibrosis. It has been reported that increased oxidative stress plays an important role in the development of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), liver fibrosis/ cirrhosis, end-stage renal disease, and cardiovascular disease [32][33][34][35][36]. The main mechanism of development of fibrosis as a cause of oxidative stress is thought to be in a consequence of oxidative stress which led to increased secretion of TGFb.…”