A large proportion of people with COVID-19, particularly severe COVID-19, develop acute kidney injury (AKI). In this feature, we review the existing research on the links between COVID-19 and kidney health.
One of the most studied serious complications associated with COVID-19 is acute respiratory distress syndrome (ARDS), which develops when someone is not getting enough oxygen. ARDS can be life threatening.
Based on recent research, about 30–40% of people hospitalized for COVID-19 develop ARDS, and close to 70% of fatal cases involve this complication.
However, as the pandemic continues, researchers are finding evidence that COVID-19 can cause a host of symptoms and lead to a number of different complications, not just ARDS. One of these is AKI, which is also known as acute renal failure.
In this Special Feature, Medical News Today explore what experts know so far about COVID-19 and AKI — including the outcome for people with both of these conditions — and what they still need to learn.
When SARS-CoV-2 infects cells, the first step is for the virus to attach to angiotensin converting enzyme 2 (ACE-2) receptors.
These receptors sit in the cellular membranes of cells lining the kidneys, lungs, gastrointestinal tract, heart, and arteries. They help moderate blood pressure by regulating levels of angiotensin, a protein that raises blood pressure by constricting blood vessels.
Some research suggests that SARS-CoV-2 may be more likely to target the kidneys than other parts of the body because ACE-2 expression is very high in the cells lining the proximal tubule. The proximal tubule is a major segment of the kidney responsible for the bulk of the reabsorption of water and nutrients from the blood.
Once SARS-CoV-2 enters kidney cells, it begins to replicate using the cell’s machinery. Cells often sustain damage during this process.
The immune system also sparks an inflammatory response once it recognizes the invading viral particles. This response can inadvertently cause further damage to healthy tissue.
AKI occurs when kidney damage is severe enough that the organ can no longer filter the blood properly. This impairment causes waste products to build up in the blood, making it harder for the kidneys to work and maintain the body’s fluid balance.
After some concerns over whether remdesivir, a drug that doctors use to treat COVID-19, may cause AKI, the European Medicines Agency (EMA) recently found no evidence of a link.
Some people with AKI may not have any symptoms at all. However, others may experience symptoms such as reduced urine output, unexplained exhaustion, and swelling around the eyes and in the ankles and legs.
In severe or untreated cases, AKI can lead to organ failure, which can result in seizures, coma, and even death.
Researchers need to collect more patient data to build their understanding of the relationship between kidney damage and COVID-19. However, most research suggests that AKI is occurring more often during the current pandemic than it did during the 2003 SARS epidemic.
Studies published in February 2021 report varied rates. According to some research, 4–37% of COVID-19 cases involve the kidneys, and AKI has an incidence of 50% in hospitalized COVID-19 patients.
A recent review paper contradicts this finding, noting that an estimated 10% of people hospitalized for COVID-19 develop AKI. Several other studies report much higher rates, though. In a study from September 2020, 81% of patients admitted to the intensive care unit (ICU) for COVID-19 developed AKI.
In comparison, during the 2003 SARS epidemic, research showed that an estimated 6.7% of people with a SARS diagnosis experienced AKI. Also, doctors diagnosed AKI as a complication in 91.7% of fatal cases.
Some factors seem to increase the risk of developing AKI with COVID-19.
For instance, age appears to play a role. In a recent subgroup analysis involving people with COVID-19, AKI affected about 12% of people in the subgroup with an average age of over 60 years. Conversely, it only affected about 6% of people in the subgroup with an average age below 60 years.
Treatments for kidney conditions, such as dialysis or immunosuppressants after receiving a kidney transplant, also weaken the immune system.
Dialysis is a process in which a machine filters a person’s blood because their kidneys can no longer perform this function. Doctors prescribe anti-rejection immunosuppressant medications to people who have undergone an organ transplant.
Both of these factors may contribute to a higher risk of severe COVID-19. Due to this, researchers and kidney organizations are calling on countries to start prioritizing people with preexisting kidney disease for COVID-19 vaccination.
Many studies have also found that race and ethnicity may influence the likelihood of developing AKI with COVID-19. In a review, 7% of people from Asia with COVID-19 experienced AKI, while its incidence among non-Asian people was 15%.
Several studies have found that Black people in the United States may be more likely to develop AKI with COVID-19.
A study in New York that included 5,449 people hospitalized for COVID-19 found that Black people were 23% more likely than white people to develop AKI after adjusting for other health factors.
Furthermore, an ample body of research shows that COVID-19 — especially a severe form of the disease — has disproportionately affected Black Americans.
Researchers note that while Black Americans make up just 12.9% of the total U.S. population, they account for roughly 25.1% of all COVID-19 deaths.
According to a 2020 paper exploring COVID-19, racism, and racial disparities in kidney disease, factors that may contribute to these disparities include:
- limited or lack of access to proper nutrition and healthcare
- racial discrimination or bias in healthcare settings
- working in “essential,” low wage jobs with a high risk of SARS-CoV-2 exposure
- living in close quarters with others where physical distancing is difficult
- economic uncertainty
- having chronic conditions, such as diabetes, heart disease, or high blood pressure
- lack of or lost health insurance coverage
- fear or mistrust of medical authorities
Being male may also increase the risk of developing AKI with COVID-19.
According to researchers, this may be because the immune system differs biologically between males and females. It could also be because lifestyle habits that weaken the immune system, such as alcohol consumption and smoking, are more common among males.
Based on the available research, it seems that AKI drastically increases the risk of severe COVID-19 and death. The reason for this is likely that AKI weakens the immune system and causes fluid imbalances, a buildup of waste in the blood, and, eventually, organ failure.
According to a recent meta-analysis, experiencing AKI with COVID-19 is associated with a 13-fold increase in mortality risk.
Recent reports from China claim that developing AKI with COVID-19 in the hospital increases the risk of death fivefold. However, the authors of the study note that rates of AKI in Western countries are much higher.
In a study from October 2020, 48% of people who had AKI and were in the ICU with COVID-19 died in the hospital. In addition, 56% of people with kidney injury required dialysis.
A 2021 study that followed 5,216 military veterans with COVID-19 also found that 32% of participants developed AKI, and 12% required kidney replacement therapy.
In the same study, AKI increased the risk of patients having to undergo mechanical ventilation significantly (about 6.5 times) and increased hospital stays by 5.56 additional days. Having AKI with COVID-19 also increased the odds of dying in the hospital sevenfold.
In a recent review, the mortality rate among people with SARS and AKI was 86.6% compared with a rate of 76.5% among those with COVID-19 and AKI. During the 2003 SARS outbreak, AKI was listed as a complication in 91.7% of fatal cases.
According to some studies, the number of people developing AKI with COVID-19 may be declining. In one study, AKI rates fell from 40% to 27% from March to July 2020.
One of the most important questions that researchers must tackle now is whether there are ways to reduce the risk of developing AKI with COVID-19. Doing this will require carefully monitoring COVID-19 patients for early signs of renal distress and treating it aggressively to prevent further damage.
Researchers also need to assess how people recover in the long term after experiencing AKI with COVID-19. Some research indicates that just as with COVID-19, some people experience unresolved symptoms or chronic symptoms after developing AKI.
In a 2021 study, some 47% of people with COVID-19 and AKI had unresolved AKI when the hospital discharged them. Other studies note that people who have experienced AKI and COVID-19 often require continual kidney support after discharge.
To gain meaningful, widely applicable data, researchers will also need to perform more rigorous, diversified research.
Currently, a disproportionate number of studies include large numbers of people at a higher risk of developing AKI, such as males, Black people, and individuals with preexisting chronic health conditions, including kidney disease.
Many studies also only focus on Western or European countries, overlooking data from large regions of Africa, South America, the Middle East, and Southeast Asia.
If scientists can answer these questions, the information could provide healthcare providers with new ways to help limit severe COVID-19 complications and reduce the risk of death.
It could also help identify individuals and populations that the authorities should prioritize for vaccination, potentially preventing severe cases before they even develop.
These discoveries would be welcome findings, especially to the millions of people worldwide with preexisting kidney disease. In the U.S. alone, an estimated 37 million people have CKD, although about 90% of them are unaware that they have it.
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