Research identifies new treatment targets to halt loss of kidney function

06 June 2025

In a study published in Nature Communications, Dr Bryan Conway and his team at the University of Edinburgh, with funding from Kidney Research UK, have identified a group of cells in the kidney that emerge during chronic kidney disease (CKD) or after acute kidney injury (AKI), leading to loss of kidney function. This work has also uncovered two promising new treatment targets that have the potential to prevent people with AKI from developing CKD and stop the decline in kidney function in people who are already affected by CKD. 

The research team, two females and two males, standing together in their research lab.

Research team (L-R) Rachel Bell, Laura Denby, Max Reck and Bryan Conway.

Mapping the kidneys in health and disease

The kidneys are made up of many different cell types which work together to remove waste products, balance fluids, salts and minerals in the body and make hormones. In CKD, and after AKI, this well-organised system of cells can get disrupted.  

Recent advances mean that researchers are now able to study individual kidney cells in detail, allowing them to create maps of the kidneys in health and disease.

The proximal tubules are tiny tubes in the kidney used to carry fluid which eventually forms urine. The proximal tubule cells have a crucial role in bringing essential nutrients, minerals and fluid back into the bloodstream and getting rid of substances not needed by the body into the urine. Previous studies using laboratory models have shown in kidney injury and AKI a group of cells within the proximal tubule transform and begin to produce signals that promote damage in the kidney.

Why is scarring in the kidney important?

Damage to the kidneys from injury or disease can sometimes be repaired by the body’s normal healing response. However, in some cases scar tissue replaces normal kidney tissue. This means that some kidney function is lost, potentially leading to chronic kidney disease (CKD).   

Finding the pathways responsible for kidney damage

The team wanted to find out whether the same changes happen to the proximal tubule cells in human kidneys as the laboratory models after AKI and in CKD.

They studied individual cells in kidneys from patients who had a kidney removed because of a tumour. In some patients, the tube draining urine from the kidney (the ureter) was blocked by the tumour, which led to inflammation and scarring. Bryan compared the cells from these kidneys with those from healthy kidney tissue where the ureter was not blocked.

An image of cells, wich has a black background and then lots of little purple dots and some which have bridge yellow around them.

An immunofluorescence image of the kidney where grey is healthy tubules and light blue show inflammatory tubules. The yellow represents scar-producing cells that are mainly located around the inflammatory tubules.

Preventing declining kidney function

Bryan noted: “We were able to see which genes are switched on and off in each kidney cell type and how the cells communicate with each other. Excitingly, we found that in both settings, like in the laboratory models of kidney injury and CKD, some cells in the proximal tubule had undergone a change that promoted damage.”

The results also showed that these cells also switched on genes usually seen in senescent cells, which can accumulate in the kidney following injury or during aging. They showed that a transcription factor (a protein that helps control switching genes on or off) called AP-1 plays a key role in the transformation of these cells.

The team then tested two different treatments – a drug that blocks AP-1, and a drug that removes senescent cells – and found that both strategies reduced inflammation and scarring in laboratory models of AKI. These exciting results highlight two new treatment targets to prevent patients with AKI from developing CKD, and to prevent declining kidney function in patients with CKD. 

What does this mean for kidney patients?

By understanding the mechanisms that lead to loss of healthy kidney cells following injury, this research could help researchers to find new treatments that prevent long term loss of kidney function after AKI.

“Support from Kidney Research UK has allowed us to understand more about the cell mechanisms that happen across different kidney diseases and how disease progresses. We have examined two potential therapeutic approaches and can take this knowledge further to develop targeted and personalised treatment strategies that slow the decline of kidney function.” Dr Bryan Conway.

Elaine Davies, director of research operations at Kidney Research UK commented: “Harnessing the potential of early intervention to prevent chronic kidney disease is a key priority for Kidney Research UK. These findings suggest that a specific subset of cells are important in kidney disease progression and further research in this area could lead towards the development of preventative treatment strategies for patients.”