Overview

Chronic kidney disease (CKD) is a progressive loss of kidney function that results in the patient depending on dialysis, transplantation, or renal replacement therapy to survive. It is characterised by kidney damage or an estimated glomerular filtration rate (eGFR) of less than mL/min/1.73 m² that has persisted for longer than 3 months, regardless of the pathology.¹

The role of the heart is to pump oxygenated blood around the body continuously. The kidneys receive 20% of the cardiac output, through the renal arteries. The role of the kidneys is to filter this blood by extracting waste, in the form of urine, as well as useful substances such as glucose and some salts, so they can be reabsorbed back into the bloodstream.²

The close relationship between these two organs means that heart enlargement, also known as cardiomegaly, can have a significant influence on the progression of kidney disease through several mechanisms, which will be explained in this article.

Understanding chronic kidney disease

CKD is a long-term condition in which the kidneys no longer efficiently filter waste and fluid from the blood. It is defined as a persistent abnormality in kidney structure or function (eGFR <60 mL/min/1.73 m² for over 3 months). A major issue with this disease is that less than 5% of patients with early CKD are unaware of their disease, often due to a lack of noticeable or non-specific symptoms initially, which leads to a delayed diagnosis and treatment and, therefore a worse prognosis.³

The most common causes of CKD are:⁴

• Diabetes
• High blood pressure
• Heart disease
• Heart failure
• Obesity
• Old age
• Family history
• Smoking 

More often than not, CKD is a multifactorial disease that combines physical, environmental, and social factors. Early stages of CKD are typically asymptomatic, but in later stages of the disease, where the eGFR decreases as the stage (1-5) increases, symptoms include:¹

• Nausea
• Vomiting
• Hypertension
• Fatigue and weakness
• Decreased focus
• Chest pain
• Shortness of breath

Knowing the symptoms of CKD allows for relatively early intervention of the disease because it allows doctors to quickly prescribe medications that are adjusted to the patient’s eGFR levels and manage risk factors to prevent further progression.

What is heart enlargement?

Heart enlargement, or cardiomegaly, is defined when the cardiothoracic ratio is over 50%. It is mainly a result of an underlying health condition such as cardiomyopathy. Initially, it is a compensatory mechanism, by which the heart is remodelled so it is stronger to pump blood to meet the body’s demands. However, over time, this causes thinning and stretching of the heart muscle, reducing its ability to pump blood around the body effectively. Therefore, this is a precursor to heart failure.⁵

How are chronic kidney disease and heart enlargement linked?

Cardiorenal syndrome is a term that describes a range of disorders, whereby the dysfunction of the heart (in this case cardiomegaly) can lead to the dysfunction of the other (chronic kidney disease) or vice versa. This section will describe two risk factors that exacerbate both CKD and heart enlargement.

Hypertension

Hypertension plays a detrimental role in the development and progression of both CKD and heart enlargement. Factors such as obesity, diabetes, smoking, kidney disease, and heart disease cause it. Persistent hypertension increases the pressure within the vasculature of the kidneys, which precedes glomerular hypertension. Over time, this can lead to glomerulosclerosis, wherein the ability of the kidneys to filter substances declines. This is represented by a poor eGFR rate which indicates the ability of the kidneys to regulate blood pressure is jeopardised.⁶ This worsening of kidney function can further aggravate hypertension by activating the renin-angiotensin-aldosterone system (RAAS). Sustained RAAS activation causes an increase in sodium and water retention, which increases the overall volume of the blood. Moreover, it stimulates vasoconstriction, which increases blood pressure. This increases the workload of the heart because it has more blood volume to pump, contributing to the remodelling of the heart to become more muscular and pump more blood.⁷

Between 50-70% of patients with CKD experience left ventricular hypertrophy (LVH) since this is the region of the heart that has to be remodelled to meet the demands of the body. This is particularly dangerous because it impairs the heart’s ability to relax and fill up with blood properly, leading to heart failure.⁸

Overall, hypertension caused by the aforementioned risk factors worsens kidney function, which in turn, increases hypertension, triggering the remodelling of the heart and LVH, a type of heart enlargement. 

Diabetes

Approximately 40% of patients with diabetes experience CKD. People with diabetes cannot produce insulin, which is supposed to turn glucose in their blood into energy. This can cause high blood sugar and damage blood vessels in both the kidneys and the heart. It increases the likelihood that fatty deposits build up in the blood vessels as plaque, which narrows the blood vessels and therefore reduces the ability of blood to reach these organs. Regarding the kidneys, this reduces the blood flow to them, which over time causes the glomeruli (subunits of the kidney that filter substances) to become less efficient at performing their function, contributing to CKD.  In addition, this reduction in eGFR also drives hypertension as mentioned previously.⁹

Concerning the heart, diabetes causes hyperinsulinemia, a compensatory mechanism to try and overcome insulin resistance.¹⁰ This promotes cardiac remodelling by stimulating cardiac muscle cells to grow, contributing to hypertrophy and, hence heart enlargement.¹¹

How can heart enlargement be managed?

ACE Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors commonly treat heart enlargement, CKD, and diabetes. This works to restore arterial blood flow pressure because the activity of angiotensin normally produces angiotensin II, which causes vasoconstriction and, therefore, higher blood pressure. Inhibition of this process means the blood vessels in the body are under less stress and reduces the workload of the heart, improving its function. Additionally, glomeruli receive more blood which allows them to improve their eGFR again.¹²

Beta-blockers

Similarly to ACE inhibitors, this class of drugs works to slow the decline of heart-related diseases that exacerbate heart enlargement and CKD. They prevent blood pressure from increasing by binding to beta-2 receptors found on smooth muscle cells. Consequently, these cells relax and enable the blood vessels to widen, reducing blood pressure and, hence, the workload on the heart.¹³

How can chronic kidney disease be managed?

Due to the cardiorenal aspect of this disease, CKD management is accompanied by reducing cardiovascular complications such as high blood pressure. Thus, ACE inhibitors and beta-blockers can be administered to patients with CKD. Treatments for end-stage kidney disease warrant life-changing procedures:

Dialysis

Dialysis enables people with end-stage kidney disease to live for many years. It is a machine that carries out the function of the kidneys - filtering out harmful and excessive substances from the patient’s body. Therefore, it is a form of renal replacement therapy, mainly used by people who also are not candidates for a transplant. However, this management of CKD comes with significant lifestyle changes. At home, patients may have to spend between 3 and 6 nights per week connected to a home haemodialysis machine. Additionally, each session would require between 6-8 hours to mimic the functions of the kidneys. Some patients may instead be required to visit the hospital for this, which is significantly time-consuming and can interfere with the patient’s social life.¹⁴

Kidney transplant

A kidney transplant is the most desired form of renal replacement therapy for patients with end-stage kidney failure. However, the limiting factor for this procedure is the number of compatible donors. Thus, only 2.5% of patients undergo a renal transplant as their first treatment procedure.¹⁵

This treatment is associated with reduced mortality and a better quality of life compared to depending on dialysis as a renal replacement therapy. The risk that the patient’s immune system rejects the donor organ means that the patient must take immunosuppressive medication for the rest of their life. The kidney transplant median survival rate has increased over the past few decades, with it being 12.1 years between 1995 and 1999. Between 2014 and 2017, survival increased to 19.2 years, demonstrating how effective this treatment has become as time progresses.¹⁶

Summary

Chronic kidney disease is a progressive failure of the kidneys that can be caused by heart enlargement or can directly cause heart enlargement. An example of the relationship between both conditions is diabetes, which due to plaque formation, can narrow the blood vessels, increasing blood pressure and therefore causing the heart to enlarge to meet the increased workload. Treatments for heart enlargement and CKD are similar due to their cardiorenal relationship. The most favourable treatments for heart enlargement are ACE inhibitors or beta-blockers which also work to treat CKD. The most favourable treatment of CKD is a renal transplant, enabling recipients to live for several more decades.