COVID-19 survivors exhibited substantially increased risk of adverse kidney outcomes in the post-acute phase, found an analysis of 1.7m US military veterans’ records, in the Journal of the American Society of Nephrology. Because many with reduced kidney function do not experience pain or other symptoms, “it’s important that physicians caring for post-COVID patients really pay attention to kidney function and disease”, said the lead author.
Since the beginning of the pandemic, doctors have found that people who become very ill with COVID-19 often experience kidney problems, not just the lung impairments that are the hallmark of the illness. This large new study suggests that kidney issues can last for months after patients recover from the initial infection, and may lead to a serious lifelong reduction of kidney function in some patients.
The study, published in the Journal of the American Society of Nephrology (JASN), found that the sicker COVID patients were initially, the more likely they were to experience lingering kidney damage.
But even people with less severe initial infections could be vulnerable. “You see across the board a higher risk of various important kidney-associated events,” said Dr F Perry Wilson, a nephrologist and associate professor of medicine at Yale, who was not involved in the study, told The New York Times. “And what was particularly striking to me was that these persisted.”
The study, based on records of patients in the Department of Veterans Affairs health system, analysed data from 89,216 people who tested positive for the coronavirus between 1 March 2020, and 15 March 2021, as well as data from 1,637,467 people who were not COVID patients.
Between one and six months after becoming infected, COVID survivors were about 35% more likely than non-COVID patients to have kidney damage or substantial declines in kidney function, said Dr Ziyad Al-Aly, chief of the research and development service at the VA St Louis Health Care System and senior author of the study.
“People who have survived the first 30 days of COVID are at risk of developing kidney disease,” said Al-Aly, who is also a nephrologist and assistant professor of medicine at Washington University School of Medicine.
Because many people with reduced kidney function do not experience pain or other symptoms, “whatʼs really important is that they realise the risk is there and that physicians caring for post-COVID patients really pay attention to kidney function and disease”, he said.
The two sets of patients in the study differed, in that members of one group had all been infected with COVID and members of the other group may have had a variety of other health conditions. Experts cautioned that there were limitations to the comparisons.
The researchers tried to minimise the differences with detailed analyses that adjusted for a long list of demographic characteristics, pre-existing health conditions, medication usage and whether people were in nursing homes. Another limitation is that patients in the VA study were largely male and white, with a median age of 68, so it is unclear how generalisable the results are.
One strength of the research, experts said, is that it involves more than 1.7 million patients with detailed electronic medical records, making it the largest study so far on COVID-related kidney problems.
While the results probably would not apply to all COVID patients, they show that for those in the study, “thereʼs a notable impact on kidney health in survivors of COVID-19 over the long term, particularly those who were very ill during their acute illness,” said Dr C. John Sperati, a nephrologist and associate professor of medicine at Johns Hopkins, who was not involved in the study.
He and other experts said that if even a small percentage of the millions of COVID survivors in the United States developed lasting kidney problems, the impact on health care would be great.
To assess kidney function, the research team evaluated levels of creatinine, a waste product that kidneys are supposed to clear from the body, as well as a measure of how well the kidneys filter the blood called the estimated glomerular filtration rate.
Healthy adults gradually lose kidney function over time, about 1% or less a year, starting in their 30s or 40s, Wilson said. Serious illnesses and infections can cause more profound or permanent loss of function that may lead to chronic kidney disease or end-stage kidney disease.
The study found that 4,757 COVID survivors had lost at least 30% of kidney function in the year after their infection, Al-Aly said.
That is equivalent to roughly “thirty years of kidney function decline”, said Wilson. COVID patients were 25% more likely to reach that level of decline than people who had not had the illness, the study found.
The New York Times reports that smaller numbers of COVID survivors had steeper declines. But they were 44% more likely than non-COVID patients to lose at least 40% of kidney function and 62% more likely to lose at least 50%.
End-stage kidney disease, which occurs when at least 85% of kidney function is lost, was detected in 220 COVID patients, Al-Aly said. COVID survivors were nearly three times as likely to receive the diagnosis as patients without COVID, the study found.
Al-Aly and his colleagues also looked at a type of sudden renal failure called acute kidney injury, which other studies have found in up to half of hospitalised COVID patients. The condition can heal without causing long-term loss of kidney function. But the study found that months after their infection, 2,812 COVID survivors suffered acute kidney injury, nearly twice the rate in non-COVID patients, Al-Aly said.
Wilson said the new data supported results of a study of 1,612 patients conducted by him and colleagues that found COVID patients with acute kidney injury had significantly worse kidney function in the months after leaving the hospital than people with acute kidney injuries from other medical conditions.
In the latest study, researchers did not directly compare COVID survivors with people infected with other viruses, like flu, making it hard to know “are you really any sicker than if you just had another bad infection”, Sperati said.
In a previous study by Al-Alyʼs team, however, which looked at many post-COVID health issues, including kidney problems, people hospitalised with COVID-19 were at significantly greater risk of developing long-term health problems in virtually every medical category, including cardiovascular, metabolic and gastrointestinal conditions, than were people hospitalised with flu.
Every type of kidney impairment measured in the new study was much more common in COVID patients who were sicker initially — those in intensive care or who experienced acute kidney injury in the hospital.
People who were less ill during their COVID hospitalisation were less likely to have lingering kidney problems, but still considerably more likely than non-COVID patients.
The study also found that even COVID patients who never needed hospitalisation had slightly higher risk of kidney trouble than the general VA patient population. But the risk seemed so small, Sperati said, that “I donʼt know that I would hang my hat on” those results.
Wilson noted that some COVID patients who did not need hospitalistion were nonetheless quite ill, needing to stay in bed for days. He said itʼs possible that those were the ones who developed long-term kidney dysfunction, rather than people at the mildest end of the COVID spectrum.
Doctors are unsure why COVID can cause kidney damage, according to The New York Times report.
Kidneys might be especially sensitive to surges of inflammation or immune system activation, or blood-clotting problems often seen in COVID patients may disturb kidney function, experts said. Sperati said COVID patients in the hospital seemed to have greater need for dialysis, and more protein and blood in their urine, than patients with other severe illnesses.
“COVID is probably a little more of a kidney-toxic virus,” Wilson said. “I do think that the COVID syndrome has some long-term adverse effects on the kidneys.”
Kidney Outcomes in Long COVID
Benjamin Bowe, Yan Xie, Evan Xu and Ziyad Al-Aly
Published in the Journal of the American Society of Nephrology September 2021,
Background: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems — referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available.
We built a cohort of 1,726,683 US veterans identified from March 01, 2020 to March 15, 2021 including 89,216 30-day COVID-19 survivors and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE) defined as eGFR decline ≥50%, ESKD, or all-cause mortality using inverse probability weighted survival regressions, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates including diagnoses, medications, and laboratory tests. Linear mixed models characterised intra-individual eGFR trajectory.
Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR=1.94 (95%CI: 1.86,2.04)), eGFR decline ≥30% (1.25 (1.14,1.37)), eGFR decline ≥40% (1.44 (1.37,1.51)), eGFR decline ≥50% (1.62 (1.51,1.74)), ESKD (2.96 (2.49-3.51)), and MAKE (1.66 (1.58,1.74)). There was a graded increase in risks of post-acute kidney outcomes according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared to non-infected controls, 30-day COVID-19 survivors exhibited excess eGFR decline of -3.26 (-3.58, -2.94), -5.20 (-6.24, -4.16), and -7.69 (-8.27, -7.12) mL/min/1.73m2/year in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection.
COVID-19 survivors exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should involve attention to kidney disease.
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