Prior COVID infection increases kidney disease risk

Approximately one in seven adults in the United States has kidney disease, where the organs responsible for filtering waste and excess water from the blood are damaged, according to the Centers for Disease Control and Prevention. Over time, this condition can lead to kidney failure, heart attack and stroke. But as many as 90% of people with chronic kidney disease don't know that they have the condition because there are often no symptoms during the early stages of the disease.

"Most people aren't diagnosed until the disease has progressed to an advanced stage. We need a better way to predict who is at risk, who is more likely to develop kidney disease so that we can detect and intervene earlier," said Djibril Ba, assistant professor of public health sciences at Penn State College of Medicine.

Now, Ba and a team of researchers from Penn State College of Medicine, have found that previous COVID-19 infection is a significant risk factor for kidney disease. Specifically, compared to influenza, those with a history of COVID-19 infection have a 2.3-times higher risk of acute kidney injury and a 1.4-times higher risk of chronic kidney disease, according to an analysis of over three million patients available online now ahead of publication in the journal Communications Medicine. They are also 4.7 times more likely to experience kidney failure.

The team developed machine learning models that incorporate COVID-19 infection history as one of nine variables used to determine who is at risk for kidney disease, which they described in a previous paper published in eBioMedicine. The researchers' new models were better able to detect individuals at risk for acute and chronic kidneys disease compared to prior models, even with fewer variables. Previous prediction models for kidney disease typically include 20 to 30 variables, none of which previously incorporated COVID-19.

"While we're in the post-pandemic era, this shows that COVID-19 history is an important variable when considering the long-term impact of the infection on kidney function and disease," said first author Yue Zhang, who received his doctorate in epidemiology from Penn State College of Medicine and is currently a postdoctoral scholar at Johns Hopkins Bloomberg School of Public Health.

According to the researchers, this is the first large-scale study to investigate the relationship between COVID-19 and kidney disease among a broad population and that compares the associations with influenza, another common viral infection. The findings align with case reports and observational studies that have suggested that COVID-19 increases risk of kidney disease as well as other studies examining the relationship within specific populations, such as hospitalized patients.

The researchers analyzed data of over three million working age adults in the United States from between 2020 and 2021 gather from MarketScan, a national database of de-identified commercial health insurance claims. Individuals were divided into three groups: those who had a history of COVID-19 infection, those who had a history of influenza but not COVID-19 and those with no history of either infection. People who were previously diagnosed with kidney disease were excluded from the analysis.

Researchers then followed the individuals between 180 and 540 days, with a median follow-up of 324 days, looking for emergence of new acute or sudden, short-term kidney injury, chronic kidney disease and end-stage renal disease where dialysis or a transplant is required. The flu cohort was included to determine if kidney issues were a common result of viral respiratory infections or if they were unique to COVID-19. Participants were matched based on age, sex, geographical region and timing of infection to account for different variants of virus.

Both types of viral infections can influence kidney health, the researchers said, but the effect of the flu was mild and temporary. COVID-19, on the other hand, had a more sustained effect, increasing the risk of acute kidney injury, which can develop within a few hours to a few days, as well as longer-term chronic and end-stage kidney disease.

The researchers explained that other studies have observed potential pathways that could explain why SARS-CoV-2 - the virus that causes COVID-19 - may target the kidneys, making the organ more susceptible to injury and disease. Kidney cells express high levels of the primary protein receptors that SARS-CoV-2 uses to enter and infect cells. Kidney cells also produce specialized enzymes that help viruses enter cells.

"Individuals with COVID-19 infection may need more frequent and more prolonged monitoring of their kidney function to enable earlier detection and possible preventative interventions," said Nasr Ghahramani, J. Lloyd Huck Chair in Medicine, professor of medicine and of public health sciences at Penn State College of Medicine and coauthor on the study. "This is particularly important for individuals who have predisposing factors for kidney disease such as diabetes and high blood pressure."

The research team plans to continue to test and refine the machine learning models and potentially to develop an application that clinicians can use to identify patients at risk for developing kidney disease.

Vernon Chinchilli, distinguished professor of public health sciences at Penn State College of Medicine also contributed to the paper.

Funding from the Artificial Intelligence and Biomedical Informatics Pilot Funding from Penn State College of Medicine supported this work.