COVID-19 and Kidney Disease – What Do We Know Now?

We’re now a year and a half into the global pandemic that is COVID-19. A virus that has changed the way we live, work, connect with family and friends, access healthcare, travel, and learn. A year ago, we wrote an article about COVID-19 and kidney disease so we thought it was time for an update, to review what we’ve learned about COVID-19 and the effect it can have on the kidneys and those with kidney disease.

COVID-19 affects people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization while others develop severe disease which may result in death.

So why does COVID-19 affect people so differently?

In severe COVID-19, the checks and balances that usually control the immune system seem to be altered. Generally, the damage to the body’s organs is not caused by the virus itself but by the immune system’s response to the virus.

A study from the University of Cambridge found that early in the infection, the immune systems of people with severe COVID-19 produced higher levels of inflammatory cytokines such as TNF-alpha, compared to people with mild disease. Those with severe disease also had fewer immune cells that are known to specifically target the virus, such as T cells and B cells. In other words, early in infection, the people with severe disease had lower numbers of immune cells that could target the virus and they had higher levels of inflammation.

On the other hand, patients with mild disease or no symptoms at all were found to mount an early and robust adaptive immune response to the virus. An adaptive immune response is where the immune system identifies an infection and then produces T cells, B cells, and antibodies specific to the virus to fight back.

Risk factors for severe COVID-19

• Age is the strongest risk factor
• Chronic kidney disease
• Cancer and certain blood disorders
• COPD
• Diabetes
• Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
• Obesity (BMI of 30 or above)
• Pregnancy and recent pregnancy
• Smoking, current or former
• Weakened immune system (eg. organ transplant, cancer treatment, long-term use of immunosuppressant drugs)

https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html

Risk of severe COVID-19 increases as the number of underlying medical conditions increases in an individual.

https://pubmed.ncbi.nlm.nih.gov/33340043/

In people with CKD those on dialysis are at highest risk, followed by people who have had a kidney transplant, then those with stage 4-5 CKD, and finally those with stage 3 CKD. There is less information about the potential for severe COVID-19 infection in people with stage 1-2 CKD.

Why do people with CKD have a higher risk of severe COVID-19 infection?

There are several suspected reasons why people with CKD may be at a higher risk of severe COVID-19.

CKD is characterized by a state of chronic inflammation, which is further enhanced by additional comorbidities such as obesity and diabetes. Persistent inflammation leads to dysfunctional responses to pathogens (viruses & bacteria). Inflammation is also tightly linked to oxidative stress, a state of imbalance between oxidant radicals and antioxidant systems. The degree of oxidative stress is directly correlated with CKD stage and peaks in patients on dialysis.

COVID-19 infection frequently triggers a massive release of proinflammatory cytokines (eg. IL-6 and TNF-a) which are responsible for organ damage and the presence of various symptoms. It makes sense then that those inflammatory responses elicited by COVID-19 are even more damaging in people who already have a high degree of inflammation.

COVID-19 is characterized by a hypercoagulable state which means there’s an increased tendency to develop blood clots (thrombus) within the body. CKD is also a prothrombotic condition which further increases the clotting risk which may result in increased cardiovascular morbidity and mortality.

CKD is believed to cause baseline lymphopenia which may play a role in the greater disease severity of COVID-19 in patients with CKD. Lymphopenia is a state of reduced lymphocytes which are one of three types of white blood cells and are our body’s first-line immune defense against disease-causing pathogens such as COVID-19. This means that people with CKD may have reduced ability to fight against COVID-19.

People with CKD often have other chronic health conditions such as diabetes and cardiovascular disease which have also been linked to a higher risk of developing severe COVID-19.

People with CKD are at a higher risk of developing Acute Kidney Injury (AKI) which also increases the risk of more severe disease.

Can COVID-19 cause damage to the kidneys?

https://www.karger.com/Article/Pdf/512683

Evidence accumulating over time showed that although COVID-19 infection primarily causes respiratory illness, other organs may be damaged by the virus, the kidneys being one of these organs.

When COVID-19 affects the kidneys, symptoms can range from proteinuria (protein in urine), haematuria (blood in urine) to severe acute kidney injury (AKI) requiring dialysis.

Exactly why COVID-19 infection causes kidney damage isn’t completely understood but it may be due to direct damage to the kidneys caused by the COVID-19 virus or the systemic effects of COVID-19 which can result in damage to the kidneys.

According to research, the viral load in the kidneys can’t wholly explain the extensive kidney damage that can occur in people with severe COVID-19 infection, so the systemic effects of COVID-19 likely play a large role.

There are a variety of different mechanisms that can lead to kidney damage and AKI in people with COVID-19 including:

Excessive Inflammatory Response

Massive viral replication may result in an excessive immune response leading to a severe inflammatory response with the production of a high level of inflammatory cytokines which cause damage to the body. This excessive immune reaction and ‘cytokine storm’ can cause kidney damage. In some people, immune complexes can also become deposited in the kidneys causing damage.

Endothelial Cell Injury

The endothelium is a thin membrane that lines the inside of the heart and blood vessels. Injury can also occur to the endothelial cells that line the glomeruli of the kidneys causing kidney damage and dysfunction.

Thrombus formation

COVID-19 can make blood cells more likely to clump and form clots. While large clots can cause heart attacks and strokes, much of the damage caused by COVID-19 is believed to stem from very small clots that block tiny blood vessels (capillaries) throughout the body. This may result in the formation of clots in the kidneys resulting in kidney damage.

Hyponatremia and Oedema

Some patients with severe COVID-19 infection experience fluid in their extremities and lungs and some develop severe hyponatremia which is low sodium levels in the blood. This suggests that these patients have water and salt metabolism disorder which is a strong risk factor for AKI.

Hypoxia of the Kidneys

Because the lungs are the main target organ of COVID-19 this can lead to hypoxia or reduced oxygen levels. In the kidneys, hypoxia may contribute to AKI because blood flow and oxygen delivery to the kidneys is reduced.

Hypovolaemia

Hypovolaemia, also known as volume depletion, is a state of abnormally low extracellular fluid in the body. This may occur from fluid loss due to diarrhea or high temperatures. Hypovolaemia results in reduced blood flow to the kidneys and is a risk factor for developing AKI.

Nephrotoxic medications

Patients with severe COVID-19 infection are often exposed to nephrotoxic medications as part of their clinical care, in particular, antibiotics, which can cause tubular injury or acute interstitial nephritis and increase the risk of developing AKI.

How common is AKI among patients with COVID-19?

Initial reports indicated that rates of AKI were negligible however, growing evidence has demonstrated that AKI is in fact common among patients with COVID-19, particularly among patients in the intensive care unit (ICU).

The reported incidence of AKI among patients with COVID-19, especially those who are hospitalized, varies depending upon the severity of the disease in the patients who are studied. In two large observational studies of over 5000 patients hospitalized with COVID-19, AKI was noted among 32 to 37% of patients. Among the patients with AKI, approximately half had mild disease (1.5 to 2-fold increase in creatinine), and the remaining had moderate or severe disease (more than doubling of creatinine). AKI requiring dialysis was noted in 12% to 15% of patients. Approximately one-half of the patients with AKI did not achieve complete recovery of their kidney function by hospital discharge.

https://pubmed.ncbi.nlm.nih.gov/32416116/

In a follow-up study of 143 people who had developed new onset kidney disease as a result of AKI during COVID-19 infection, 91% of these patients had recovered from this new onset kidney disease after 4 months.

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06105-8

This is obviously only one small study so more; longer-term studies are needed to determine what percentage of patients with COVID-19 end up developing CKD as a result of COVID-19 infection.

People with pre-existing CKD are at a greater risk for developing AKI and having CKD can affect kidney repair and recovery from AKI which means they may experience a worsening of the kidney disease following COVID-19 infection.

Other organ damage caused by COVID-19

The kidneys are not the only organs that may be damaged by COVID-19 infection and organ damage from COVID-19 may increase the risk of long-term health problems. Organs that may be affected by COVID-19 include:

• Heart: Imaging tests taken months after recovery from COVID-19 have shown lasting damage to the heart muscle, even in people who experienced only mild COVID-19 symptoms. This may increase the risk of heart failure or other heart complications in the future.

• Lungs: The type of pneumonia often associated with COVID-19 can cause long-standing damage to the tiny air sacs (alveoli) in the lungs. The resulting scar tissue can lead to long-term breathing problems.

• Brain: Even in young people, COVID-19 can cause strokes, seizures, and Guillain-Barre syndrome- a condition that causes temporary paralysis. COVID-19 may also increase the risk of developing Parkinson’s disease and Alzheimer’s disease.

Other Long-term effects of COVID

Most people who have COVID-19 recover completely within a few weeks. But some people- even those who had mild versions of the disease- continue to experience symptoms after their initial recovery.

This has been called post-COVID-19 syndrome or ‘long COVID-19.’ These health conditions are sometimes called post-COVID-19 conditions. They’re generally considered to be effects of COVID-19 that persist for more than four weeks after you’ve been diagnosed with the COVID-19 virus.

Post-COVID conditions are a wide range of new, returning, or ongoing health problems people can experience four or more weeks after first being infected with the virus that causes COVID-19. Even people who didn’t have COVID-19 symptoms in the days or weeks after they were infected can have post-COVID conditions.

Older people and people with other serious medical conditions are the most likely to experience lingering COVID-19 symptoms, but even young, otherwise healthy people can feel unwell for weeks to months after infection. Common signs and symptoms that linger over time include:

• Fatigue
• Shortness of breath or difficulty breathing
• Cough
• Joint pain
• Chest pain
• Memory, concentration, or sleep problems
• Muscle pain
• Headaches
• Loss of smell or taste
• Depression or anxiety
• Fever
• Dizziness when you stand
• Worsened symptoms after physical or mental activities

Final words

So, what does all of this mean? Obviously, avoiding COVID-19 infection is always going to be the number one priority but we know that’s not always possible so what else can you do?

Well, the benefit of knowing what factors increase the risk of developing severe COVID-19 infection is that we have a better understanding of what needs to be addressed to reduce that risk.

1. Manage and treat any underlying health conditions known to increase the risk of severe COVID-19 infection including kidney disease, diabetes, obesity, COPD, and cardiovascular disease.
2. Stop smoking
3. Support your immune system- for some tips on how to do this download our free guide- 7 Immune Boosting Natural Remedies for Kidney Disease

Remember, anything you do NOW to improve your health and your kidneys will put you in a better position regardless of what infection you may develop. And for those of you who have developed kidney disease following COVID-19 infection or have experienced a worsening of your kidney disease please know that there are plenty of tried and tested natural techniques to heal your kidneys and improve your kidney function.

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