A new approach to treat BK virus in kidney transplant patients
With support from Kidney Research UK through the Sabita Dindayal Award, Dr Peter Wing will investigate how the BK virus behaves when oxygen levels are low, with the aim of finding new BK virus treatments for patients who have received a kidney transplant.
BK virus infection in kidney transplant patients remains a significant challenge
BK virus is an infection that many people get in childhood. Although it is usually mild and does not cause long-term problems, the virus can stay in the kidneys without causing an active infection.
Transplanted kidneys need be protected from the body’s immune system using drugs known as immunosuppressants. These drugs prevent the immune system from attacking the new kidney, but they also make it weaker. In some cases, this means that BK virus can become active again.
Currently, there is no effective treatment for BK virus infection other than reducing the level of immunosuppression to allow the immune system to strengthen and fight the virus. This can lead to rejection and loss of the donated kidney as the immune system may also target the new organ.
Meet Dr Peter Wing
Dr Peter Wing, from the University of Oxford has received a Sabita Dindayal award PhD studentship of £100,000 to investigate a new approach to treating BK virus infection by looking at the levels of oxygen in kidney cells.
“BK virus infection can cause severe complications in patients with a kidney transplant, including damage to the transplant itself. As a virologist with a specialist interest in how viruses respond to low levels of oxygen, I want to understand more about BK virus biology and mechanisms so that we can be closer to developing alternative treatments to manage the risk of infection.” Dr Peter Wing.
How do kidney cells detect and respond to oxygen?
Low levels of oxygen (called ‘hypoxia’) naturally occurs in kidney disease. Peter and the team have previously found that this may allow the BK virus to thrive and replicate in kidney cells, and they now aim to understand why.
Identifying new BK virus treatments after kidney transplant
Firstly, they will monitor BK virus activity in kidney organoids (miniature lab grown models of kidneys), grown in low oxygen levels to understand how these conditions allow the virus to thrive.
By using a technique called spatial transcriptomics, which analyses which genes (regions of DNA) are turned on or off in cells in different situations, they will identify specific genes that may be driving BK virus replication.
Lastly, Peter and the team will then test a type of medicine called HIF inhibitors, previously developed to treat low iron levels (anaemia) in kidney patients, to see how they affect BK virus activity and see if they can be used as a future treatment.
What are HIF inhibitors?
HIF inhibitors are a class of drugs used to treat anaemia in patients with chronic kidney disease (CKD).
Peter and the team have previously seen that HIF inhibitors, can stop the BK virus from growing in low oxygen, levels and are now investigating this further.
What does this mean for kidney transplant patients?
This work will allow researchers to better understand how the BK virus behaves when oxygen levels are low. This could lead to future work identifying ways treating BK virus in patients with a kidney transplant.
“We understand the concerns of patients relating to the potential impact of BK virus infection on the health of their kidney transplant and there is a huge unmet need for new and effective treatments. With the Sabita Dindayal award from Kidney Research UK, we want to better understand the mechanisms that drive BK virus growth in low levels of oxygen and use this knowledge to support new treatment approaches.” Peter Wing.
Sabita Dindayal research award
Through the Sabita Dindayal Award, Sabita’s widower, Vidur, will honour her legacy by supporting research that will make a real difference in the lives of kidney patients.
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