Long COVID Could Spell Kidney Troubles Down the Line

Maureen Salamon

September 09, 2021

Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.

The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the intensive care unit (ICU) or experienced acute kidney injury (AKI) while hospitalized.

Researchers analyzed US Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online September 1 in the Journal of the American Society of Nephrology.

The risk of kidney problems "is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn't be discounted. Those people represent the majority of those with COVID-19," said senior author Ziyad Al-Aly, MD, of the VA St. Louis Health Care System, Missouri.

"That's why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial," he told Medscape Medical News. "It's smaller than in people who were in the ICU, but it's not...zero."

Experts aren't yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in angiotensin-converting enzyme 2 (ACE2) receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University School of Medicine in New Haven, Connecticut, and a member of Medscape's advisory board.

Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Al-Aly and Wilson both suggested.

COVID-19 Survivors More Likely to Have Kidney Damage Than Controls

"A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component," Al-Aly advised. "They should check patients' blood and urine for kidney problems."

This is particularly important because "kidney problems, for the most part, are painless and silent," he added.

"Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don't want. We don't want this to be unrecognized, uncared for, unattended to," he said.

Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants' estimated glomerular filtration rate (eGFR) and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.

Results were striking, with COVID-19 survivors about one third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.

Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.

If Your Patient Had COVID-19, "It's Reasonable to Check Kidney Function"

"This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it's reasonable to check their kidney function," Wilson, who was not involved with the research, told Medscape Medical News.

"Even for patients who were not hospitalized, if they were laid low or dehydrated...it should be part of the post-COVID care package," he said.

If just a fraction of the millions of COVID-19 survivors in the United States develope long-term kidney problems, the ripple effect on American healthcare could be substantial, Wilson and Al-Aly agreed.

"We're still living in a pandemic, so it's hard to tell the total impact," Al-Aly said. "But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and healthcare in the United States for a decade or more."

Because renal problems can limit a patient's treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.

"There are a lot of medications you can't use in people with advanced kidney problems," Al-Aly said.

The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9000 women were included in the VA data, Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.

The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.

"We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what's going on with their kidneys," Wilson said.

"Lastly — and a much tougher sell — is we need biopsies. It's very hard to infer what's going on in complex disease with the kidneys without biopsy tissue," he added.

The study was funded by the American Society of Nephrology and the US Department of Veterans Affairs. Al-Aly and Wilson have reported no relevant financial relationships.

J Am Soc Nephrol. Published online September 1, 2021. Abstract

Maureen Salamon is a freelance health journalist based in New Jersey whose work has appeared in The New York Times, The Atlantic, CNN.com, and other major outlets.

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