Vulnerable kidneys can’t repair

As people age, their kidneys become more susceptible to injury and less able to repair after injury, leading to scarring. This also happens in younger patients with chronic kidney disease, but we don’t know why. 

Senescent cells are alive, but they have lost the ability to divide, and they release signalling molecules that can lead to inflammation and scarring. Scientists have already discovered that senescent cells are important in the repair of other organs such as the lung and liver.  

Higher numbers of senescent cells in the kidney are linked to chronic kidney disease progression and also transplants that are more likely to fail. But until now we didn’t know if the senescent cells themselves drive poor repair and scarring. 

Senescent cells affect kidney health

Dr David Ferenbach, who led the Edinburgh team explains: “In our study, my colleague and first author Dr Katie Mylonas and the team discovered there were more senescent cells in kidneys of older and injured mice, which reflected the fact that the elderly and people with injured kidneys also have more of these cells.  

“We then went on to find that the kidneys of aged or previously injured mice recovered less well and scarred more easily than healthy kidneys after a subsequent renal injury,” he said. 

When Dr Mylonas and the team gave older or injured mice an experimental drug called ABT-263 to kill the senescent cells before injury, the kidneys became primed, there was less kidney scarring and kidneys functioned better after injury. 

Translating research into treatment

The team will now study ABT-263 in human kidneys that are too damaged to be used in transplant operations. If it works, this drug could be used to protect transplant recipients and patients with chronic kidney disease who need to have operations that carry a risk of acute kidney injury – when your kidneys suddenly fail.  

“This work shows that senescent cells are not simply harmless markers of an old or damaged kidney - they help make kidneys more vulnerable to further injury and scarring,” says David. “The next step would be to run a clinical trial to target these cells - with the goal of restoring ‘healthy, young’ behaviour to the kidneys of the elderly and those with chronic kidney disease.”  

“I have high hopes that this is a line of enquiry which we can drive all the way from test tubes and experimental models through to an important new treatment to protect patients against progression to kidney failure.” 

Dr Maria Tennant, head of communications at Kidney Research UK said: “This fascinating study reveals a new way to target senescent cells in human kidneys. We are committed to driving forward research that will transform treatments for kidney patients and this study could pave the way for new treatments to protect more kidneys, reverse the harmful scarring process and ensure transplanted kidneys work well for longer.” 

Read the full paper here.