OXIDATIVE STRESS MECHANISMS IN CHRONIC KIDNEY DISEASE

Abstract

Chronic kidney disease (CKD) is a significant health concern resulting from damage to the kidneys and ureters. CKD is characterized by a decreased glomerular filtration rate and proteinuria. Recent studies suggest that oxidative stress plays a crucial role in the pathophysiology of CKD. During CKD progression, an imbalance in free radical production leads to excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS), overwhelming the body's antioxidant defenses. This imbalance causes oxidative stress, damaging target molecules such as DNA, proteins, and lipids, ultimately leading to cell death. Evidence indicates that CKD is associated with oxidative stress, contributing to disease progression through several mechanisms: (1) mitochondrial dysfunction resulting in increased ROS production, (2) activation of NADPH-Oxidase (NOX) isoforms, a significant source of oxidative stress in the kidneys, (3) disassembly of eNOS, a key contributor to oxidative stress and kidney damage, (4) myeloperoxidase (MPO) involvement in the development and progression of kidney disease, (5) increased xanthine oxidase (XO) activity in CKD patients, (6) elevated superoxide dismutase-1 levels in dialysis patients, and (7) presence of inflammatory factors, which enhance oxidative stress and disrupt redox balance, further increasing inflammation. This oxidative stress and inflammation lead to tissue injury, disease progression, and the severity of CKD. To combat oxidative stress and mitigate clinical symptoms, drugs and antioxidants are employed, aiming to delay CKD progression and reduce its clinical impact.