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NEW YORK (Reuters Health) – SARS-CoV-2 does not seem to injure the kidney directly, but may trigger acute injury or tubular damage in already injured cells, a preclinical study suggests.

“We were surprised to see the outcome of our experiment,” Dr. Benjamin Dekel of Sheba Medical Center and Tel Aviv University in Israel told Reuters Health by email.

The human adult kidney cells the team studied “had all of the molecules required for viral entry – ACE2 and others – and indeed, we observed both infection and replication of the virus in the cells,” he said. “Much to our surprise, no evidence for cell destruction and cell death was apparent. The cell viability tests were the same for kidney cells infected and counterparts that were not infected.”

A separate comparison of human adult kidney cells to a monkey kidney cell line deficient in interferon molecules showed that in the interferon-deficient cells, “destruction and cytopathic response was clearly evident within a short period of time, accutane+zyrtec ” he noted.

“Interestingly,” he said, “the baseline levels of interferon molecules measured in the human kidney cells was relatively high. We propose that this is a protective mechanism, allowing the human kidney cells to survive invasion by the virus.”

“We were also surprised that when cells were grown in ‘injury mode,’ they were more susceptible to infection and replication of the virus and consequent inflammatory response,’ he said. “In addition, molecular markers related to kidney injury were significantly changed in these cells following viral infection, suggesting some damage caused by the virus.”

As reported in the Journal of the American Society of Nephrology, Dr. Dekel and colleagues did a series of experiments in ex vivo cell models to analyze SARSCov2 interactions with kidney tubular cells and assess direct tubular injury.

They grew primary human kidney epithelial cells derived from nephrectomies as three-dimensional spheroids that imitate the healthy kidney, and as a two-dimensional layer that mimics the cells of an acutely injured kidney.

As Dr. Dekel noted, cells that mimicked an acutely injured kidney were more prone to infection and additional injury, but not cell death, suggesting that the virus is unlikely to be a primary cause of the acute injury seen in COVID-19, and that if such injury takes place in the kidney by any cause, the virus might take the opportunity to intensify it.

Dr. Dekel said, “We suggest that if one contracts the virus and it ends up in (the) kidney cells, this would not directly or by itself lead to profound AKI or acute tubular necrosis (ATN) – i.e., no cytopathic effect/cell death observed following infection.”

“Presumably,” he added, “if AKI/ATN does occur for a variety of medical reasons and kidney cells turn to ‘injury’ mode (proliferation/de-differentiation), the virus may exploit this weakness to add some form of damage (being an additive to deteriorate renal function).”

“In hospitalized COVID-19 cases, we should try and make every effort to perfuse kidneys well and prevent the injury mode cascade,” he concluded.

Dr. Robert Greenwell, Chief of Nephrology at Mercy Medical Center in Baltimore, commented in an email to Reuters Health, “Many recognized etiologies of AKI – e.g., intravenous radiology contrast, aminoglycoside antibiotics, NSAIDS – are more likely to cause temporary kidney damage if kidney function is already stressed or functioning abnormally. Whether the risk involves reduction in kidney blood flow or reduction in certain factors like interferon, as the article suggests, is not clear.”

“To me, the study emphasizes that patients with COVID-19 infection are at risk for AKI and that we might be able to lessen that risk by trying to avoid hospital-related causes of AKI – e.g., by correcting low blood pressure with IV fluids or other medications, and trying to avoid agents that might cause AKI, (thereby) increasing the risk of COVID-related AKI.”

SOURCE: Journal of the American Society of Nephrology, online June 10, 2021.

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