What is chronic kidney disease (CKD)?

Chronic kidney disease (CKD) is a progressive and irreversible condition characterized by gradual loss of kidney function over time. The kidneys are vital organs responsible for filtering waste products, excess fluids, and toxins from the blood, regulating electrolyte balance, and producing hormones that help control blood pressure and red blood cell production. In chronic kidney disease, the kidneys become damaged and are unable to perform these functions effectively.


CKD is typically diagnosed based on a persistent decline in kidney function, as measured by a decrease in glomerular filtration rate (GFR) or the presence of kidney damage, such as proteinuria (presence of protein in the urine) or structural abnormalities detected on imaging studies. CKD is classified into five stages based on the severity of kidney damage and decline in GFR, ranging from Stage 1 (mild kidney damage with normal or increased GFR) to Stage 5 (end-stage kidney disease, or ESKD, with severely reduced GFR and kidney failure).


What is the relationship between CKD and oxidative stress?

Oxidative stress plays a central role in the pathophysiology and progression of kidney damage in CKD. Here’s how CKD and oxidative stress are related:


  • Impaired Antioxidant Defense Mechanisms: CKD is associated with disturbances in antioxidant defense mechanisms, leading to increased susceptibility to oxidative stress. The kidneys play a crucial role in regulating antioxidant balance by producing and metabolizing antioxidants such as glutathione, superoxide dismutase (SOD), catalase, and vitamin E. In CKD, there is often a depletion of antioxidants and a reduction in antioxidant enzyme activity, compromising the kidney’s ability to neutralize reactive oxygen species (ROS) and oxidative damage.


  • Mitochondrial Dysfunction: Mitochondrial dysfunction is a common feature of CKD, characterized by impaired mitochondrial structure and function. Mitochondria are the primary site of ROS production within cells, and dysfunctional mitochondria contribute to oxidative stress by generating excessive amounts of ROS. In CKD, factors such as uremic toxins, inflammation, and metabolic abnormalities can impair mitochondrial function, leading to increased ROS production and oxidative damage to kidney cells.


  • Inflammation and Immune Dysregulation: CKD is associated with a state of chronic inflammation and immune dysregulation, which contribute to oxidative stress. Inflammatory cytokines and activated immune cells produce ROS and reactive nitrogen species (RNS) as part of the immune response. Persistent inflammation in CKD leads to sustained ROS production and oxidative damage to kidney tissues, exacerbating kidney injury and fibrosis.


  • Endothelial Dysfunction: Endothelial dysfunction, characterized by impaired nitric oxide (NO) bioavailability and endothelial nitric oxide synthase (eNOS) activity, is a common feature of CKD. Reduced NO levels and eNOS uncoupling lead to endothelial dysfunction and impaired vasodilation. Oxidative stress contributes to endothelial dysfunction by scavenging NO, promoting eNOS uncoupling, and generating vasoconstrictive ROS species. Endothelial dysfunction further contributes to kidney injury, fibrosis, and progression of CKD.


  • Activation of Renin-Angiotensin-Aldosterone System (RAAS): Activation of the renin-angiotensin-aldosterone system (RAAS) is a hallmark feature of CKD and contributes to oxidative stress. Angiotensin II, a key effector of the RAAS, promotes ROS production through activation of NADPH oxidase and mitochondrial dysfunction. ROS, in turn, activate pro-inflammatory and pro-fibrotic pathways, leading to kidney injury and fibrosis. Inhibition of the RAAS with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) can help mitigate oxidative stress and slow the progression of CKD.


Overall, oxidative stress plays a critical role in the pathogenesis and progression of chronic kidney disease by contributing to mitochondrial dysfunction, inflammation, endothelial dysfunction, and activation of the RAAS.