Melbourne researchers show how COVID-19 infects the kidney

Using lab-grown kidney tissue made from human stem cells, researchers across Melbourne have, for the first time, been able show how SARS-CoV-2 enters and directly infects the kidney cells.

There is a high incidence of acute kidney disease in people hospitalised with COVID-19, caused by the SARS-CoV-2 virus infection. However, whether the virus directly infects the kidney, how it enters the tissue, and the implications of this infection, are not fully understood.

Using lab-grown kidney tissue made from human stem cells, researchers across Melbourne have now been able show how SARS-CoV-2 enters and directly infects the kidney cells, with this research published in the Journal of Virology.

Their findings have also confirmed that a common medication for high blood pressure does not increase the risk of COVID infection in the kidney.

SARS-CoV-2 infected kidney organoid
SARS-CoV-2 infected kidney organoid

Improved understanding of how SARS-COV-2 enters the kidney
The collaborative study from Melbourne research institutes, co-led by Dr Jessica Vanslambrouck, Team Leader in the Kidney Regeneration lab at Murdoch Children’s Research Institute and Associate Investigator with the Novo Nordisk Center for Stem Cell Medicine, reNEW, is the first to use stem cell-derived human kidney organoids with enhanced proximal tubules to understand the mechanisms of SARS-CoV-2 entry.

A key target of SARS-CoV-2, the kidney proximal tubules play vital roles in filtering waste products and toxins from the bloodstream, clearing them from the body in the urine while at the same time preventing the loss of essential substances like nutrients. Dr Vanslambrouck and her team have recently advanced our ability to grow kidney organoids with improved proximal tubules, which better represent human kidneys.

Using the improved kidney proximal tubule model, this study confirmed the well-known ACE2 receptor to be the sole entry receptor for SARS-CoV-2 in kidney and that the virus can then use two different pathways to complete its entry into the cells.

Effects of common medication
The team also used these human kidney models to investigate the effect of Lisinopril on SARS-CoV-2 infection.

People living with high blood pressure and related kidney disease are often prescribed Lisinopril to help protect the kidneys from further damage by reducing blood pressure and protein loss in the urine.

The results of the study demonstrate that the use of Lisinopril does not increase a person’s susceptibility to SARS-CoV-2 infection in the kidney, consistent with existing clinical research and recommendations from medical societies for patients to continue this medication.

These two findings provide deeper insights into the implications of the COVID-19 pandemic to kidney health and valuable perspectives for future treatments to reduce or prevent viral infection of the kidney.

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