The Faces of Cardiovascular Disease: Part 4

This article is part of a mini-series, The Faces of Cardiovascular Disease, looking at the different presentations, symptoms, and root causes of a disease that affects millions of men and women around the world. Be sure to read parts 1, 2, and 3 here. In this installment, we explore features of chronic kidney disease, with a focus on vascular calcification. As this series comes to a close, stay tuned for future articles focusing on other areas of Resverlogix’s ongoing research and treatment options.

We all know the feeling of exhaustion. It’s not just that you’re tired, everything becomes more difficult; it’s harder to get up, harder to get moving, harder to focus, harder to function. You feel drained.

For most of us, a really good night’s sleep, or a relaxing weekend getaway, is all it takes to rejuvenate our energy levels. However, for people with chronic kidney disease (CKD), fatigue can become a normal part of daily life. What most of us don’t realize is how dramatically constant exhaustion can affect you and those around you.

The persistent fatigue experienced by people with CKD is difficult for a healthy person to relate to, and often leaves CKD sufferers feeling misunderstood by friends, family and co-workers.

Just imagine feeling too tired to plan your spouse’s birthday – knowing that they deserve to feel special and appreciated, not feeling able to muster up the energy to attend family gatherings, even during the holidays, or being so exhausted by the end of the day that all you can think about is quitting your job. Then the guilt kicks in, and makes it all feel even worse.

Fatigue is subjective by nature. There is a stigma around complaining of tiredness. People tend to think you are lazy and unmotivated, and no one wants to be known as the “complainer”. The stigma is so strong that people with CKD will deliberately neglect to mention their fatigue, even to their doctor, and so it is commonly underreported and undertreated. But fatigue’s effects are very real, and it should be taken seriously.

Fatigue in CKD is caused by a number of disease-related factors: low red blood cell production (renal anemia), build-up of waste and toxins in the blood due to improper filtering by the kidneys, high potassium levels, high blood pressure, and calcification in blood vessels – making it more difficult for the heart to pump blood throughout the body. All of these factors are linked in CKD: they feed each other in a vicious cycle.

These same issues also contribute to cardiovascular disease (CVD). It’s well known that CKD can cause CVD, and vice versa. One of the primary drivers of CKD and related CVD is an imbalance in calcium and phosphorus levels in the body. This leads to the serious consequence of vascular calcification.


In CKD, the buildup of waste and toxins, which leads to the imbalance in calcium and phosphorus levels in the blood, creates “osteogenic” – or “bone-forming” conditions. Under these conditions, processes normally reserved for bone growth and healing are inappropriately activated in vascular smooth muscle cells, found in the middle layer of blood vessels.

Once activated, these cells transform from elastic and stretchy into rigid cells that behave like bone. Hard, calcium-rich minerals are deposited inside the blood vessel walls. This process is called vascular calcification.

Epigenetic changes are responsible for this disease-state transformation. Markers on genes that normally ensure that a vascular smooth muscle cell stays a vascular smooth muscle cell are removed, and markers on genes that drive calcification are added. As the balance shifts so does the cell’s identity – and functionality.

With stiffening of its transportation highway – vessels and arteries – blood can no longer be easily pumped throughout the body. This is particularly detrimental to the heart. The loss of elasticity in the vessels increases blood pressure and stress on the heart, and can ultimately lead to heart failure. In fact, the extent of vascular calcification in CKD can predict cardiovascular risk.

Vascular calcification, as described above, is often considered specific to CKD. However, calcification also occurs around atherosclerotic plaques as described in part 2. Together, these and many other factors significantly raise the risk of cardiovascular-related death in people with CKD.


CKD and vascular calcification take decades to develop, and often go unrecognized and undiagnosed until the disease has already destroyed the majority of kidney function. Like with many conditions, prevention and early detection are critical. Knowing the risk factors, staying active, eating well and monitoring your blood pressure are all important steps you can take.

If you are at risk, make sure you know the warning signs. The kidney foundation of Canada has made a helpful quiz to assess your risk. If you, or someone you know, are feeling chronic and extreme fatigue, see your doctor as soon as possible.

At Resverlogix, we continue to research the complex biology underlying CKD and associated cardiovascular issues, as well as other multi-factorial diseases. Our goal is to determine how we may be able to help individuals burdened by diseases such as CKD, which have so many complex and intertwined biological underpinnings.

In the final article of our series, we will discuss the latest developments in the prevention and treatment of cardiovascular disease, and what may be just over the horizon.