Cardiovascular Disease and CKD
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). (1, 2)
Why is this?
Well, the simple answer: as kidney function declines, so does the heart’s ability to pump blood.
In patients with CKD, complications such as chronic anemia, oxidative stress, and chronic inflammation can lead to thickening of the walls in the heart and blood vessels, thus increasing the risk of developing CVD. (2, 3) While the exact pathophysiology of why CVD is prevalent in patients with CKD is still being studied, research has also shown correlations between CVD in patient’s with CKD and:
impaired metabolism of calcium and phosphate, (2)
endothelial dysfunction, (2)
gut microbiome, (4)
CKD-mineral bone disease. (4)
Chronic Anemia
Studies have shown an association between heart disease and chronic anemia. (3)
The heart’s job is to circulate oxygen rich-blood throughout the blood to keep tissue alive. In chronic anemia the body is unable to produce enough red blood cells (RBC) thus less oxygen-rich blood is circulating throughout the body. In response to continuously low levels of RBC, cardiac output increases (3). In other words, the heart rate increases which can eventually lead to thickening of the walls in the heart and blood vessels.
Anemia is common in patients with CKD due to decrease production of erythropoietin, nutrient deficiencies, and blood loss related to hemodialysis treatment. The kidneys produce erythropoietin, a hormone that signals the production of red blood cells. As kidney function declines, erythropoietin levels begin to decline as well. Anemia can also occur as a result of nutrient deficiencies including iron, B12, B6, and folate which play a role in red blood cell production. Anemia is also common in patients who undergo hemodialysis due to blood loss during the treatment.
Oxidative Stress
What is oxidative stress?
Oxidative stress is the imbalance of reactive oxygen species and antioxidants.
Reactive oxygen species (ROS) are essentially highly reactive oxygen containing chemicals, aka free radicals that, when unchecked, can cause a host of damage to proteins, lipids and DNA. (2) ROS production is normal and the body has a defense mechanism to regulate ROS, aka antioxidants. The primary job of antioxidants is to find free radicals, prevent their damage or reduce the amount of damage they have on the body.
Why does oxidative stress occur in patients with CKD?
Oxidative stress can occur in patients with CKD, especially the advanced stages of CKD. Uremic toxins and bio-incompatibility to hemodialysis (HD) and peritoneal dialysis (PD) can lead to oxidative stress (4). For instance, with highly permeable membranes used in HD can result in loss of antioxidants. (4) The low pH and high osmolality of PD solutions can effectively create a reaction that leads to increased production of ROS. (4)
How is oxidative stress associated with CVD in patients with CKD?
Oxidative stress can lead to the oxidation of low-density lipoprotein (LDL) leading to buildup of plaque on the walls of arteries, aka atherosclerosis (4). Thus, increasing the risk of developing CVD.
Chronic Inflammation
Inflammation goes hand in hand with oxidative stress. Oxidative stress can lead to inflammation and inflammation can lead to oxidative stress.
Inflammation is part of the body’s defense mechanism and plays an important role in the healing process. (5) However, like oxidative stress, if gone unchecked, inflammation can become chronic and cause damage to the body including the heart.
The body can self-regulate inflammation with the help of cytokines. Cytokines are types of proteins that essentially helps “activate” the immune system. (6) Which explains why some some cytokines are used as a biomarkers for CVD as they are used to help identify the presence of inflammation in the body.
Why does inflammation occur in patients with CKD?
Patients with CKD can experience inflammation related to a multitude of factors including: (7)
malnutrition
infections related to dialysis vascular access
poor dental health
anemia
uremia
Pro-Inflammatory Cytokines & CVD
Research has shown that pro-inflammatory cytokines such as C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF) receptors I & II are not only biomarkers associated with CVD but some of these cytokines may play a role in the body’s inflammatory response system with certain types of CVD in patients with CKD. (2) For example, research shows that CRP may play a role in the development of plaque along blood vessel walls in atherosclerosis. (2, 8)
