Finding new ways to protect transplanted kidneys

20 June 2024

Professor David Ferenbach from the University of Edinburgh has received a Professor Michael Nicholson Research Project award of £250,000 to investigate a new strategy to make transplanted kidneys last for longer.

Professor David Ferenbach

“My very first grant was with Kidney Research UK and without it, I wouldn’t be in research today. As part of my investigations, I developed an interest in cell senescence and have been lucky enough to be able to continue to investigate it via ongoing fellowship and research grant support. With this recent grant award, we will test the importance of cellular senescence in kidney transplantation for the first time.” David Ferenbach.

The problem

We know that kidneys from older donors, transplanted kidneys that are slow to start working and transplanted kidneys that have come under attack from the immune system all have a higher risk of failing. Previously, doctors have tried to prevent this by increasing the medications used to suppress the immune system, but this is not always successful.

The solution

With our support, David and the team will study a process called ‘cellular senescence’.

David, and his collaborators Drs Mark Harber and Rhys Evans from London will study how senescent cells in transplanted kidneys contribute to eventual kidney failure. The team will look at senescent cells in kidney transplant samples taken at the time of transplant, 6 weeks after transplant and 1 year after transplant, and will use newly developed technologies to understand more about the signals between senescent cells, the immune system and scar-producing cells. These signals represent potential targets for future treatments.

The team will track which of the sampled kidneys went on to develop problems such as delayed or poor function or rejection, revealing whether any patterns in senescent cell presence, location or behaviour can predict how well the kidney will work in the long term. They will confirm their findings in a second set of samples from kidney transplants to confirm their ability to influence long-term transplant outcome.

All about senescent cells

Senescent cells have stopped dividing and no longer contribute to repair and growth. Cells can become senescent as part of the normal aging process, but certain conditions, including a temporary loss of blood supply or damage from the immune system (both common in transplanted kidneys) can also cause cells to become senescent. These senescent cells release signals leading to further inflammation and tissue damage. David and his team have previously shown that having more senescent cells inside a kidney worsens scarring over time.

Image credit: US Government National Institute on Aging.

What could this mean for kidney patients?

This work will help to identify which patients are at high risk of kidney transplant failure, so that they can be offered the opportunity to take part in clinical trials of therapies to prevent further kidney damage. Targeting senescent cells in transplanted kidneys is a novel treatment option with the potential to help transplanted kidneys last longer.

“We aspire to make every transplanted kidney function better for longer. This project will allow us to build on our existing work to determine if senescent cells present before or after transplantation contribute to reduced kidney function. If, as predicted, they do, they will represent an exciting target for new treatments”. David Ferenbach.