Why does focal segmental glomerulosclerosis recur after transplantation? How can we stop it?

16 June 2025

Focal segmental glomerulosclerosis (FSGS) is a term for a family of diseases involving damage to the glomeruli (the tiny filters of the kidney). It can be caused by genetic conditions or by underlying diseases, although sometimes the cause is unknown – this is known as “primary” focal segmental glomerulosclerosis (pFSGS).

With support from Kidney Research UK, Dr Katherine Bull will investigate how damage might be caused in pFSGS, with the aim of developing new treatments.

Focal segmental glomerulosclerosis (FSGS) remains a challenge for patients and healthcare professionals

For some, pFSGS usually causes nephrotic syndrome (a condition where large amounts of protein leak into the urine causing swelling) and can progress to kidney failure. Sometimes, it can come back quickly after transplantation, leading to loss of the new kidney. For these patients, a second transplant is unlikely to be successful and many FSGS patients face a lifetime of dialysis.

Currently, there are very limited treatments for pFSGS and research is made difficult by its unknown causes.

Dr Katherine Bull

Meet Dr Katherine Bull

Dr Katherine Bull, Honorary consultant nephrologist, from the University of Oxford, has been awarded a £245,000 research project grant to apply new technologies to understand what might cause damage in pFSGS and investigate new treatments to stop it from recuring after transplantation.

“We are looking at a rare disease with a devastating impact on patients. There is no cure for FSGS, and it can recur after transplantation. By looking more closely at the kidney and its patterns of injury, we hope to better understand the factors that lead to the disorder.” Katherine Bull.

Understanding how antibodies might cause damage

Antibodies are proteins made by the immune system to protect the body from potentially harmful invaders. Recently pFSGS has been linked to antibodies associated with nephrin, a protein made by kidney cells that filter blood. Some people with nephrotic syndrome and FSGS have high levels of these antibodies, and this is linked to how serious the disease is and whether it comes back after transplant.

Katherine and the team will study stored samples from the same kidney before it is transplanted, and after transplant surgery, in cases where FSGS has come back in the new kidney. Then, using a technique called spatial transcriptomics which locates and cells in the kidney and identifies which genes are turned on or off, they will make a kidney map to pinpoint targets for potential new treatments.

An image of a kidney which show multicolored cells

Spatial transcriptomics image of a kidney where the pink spheres in the centre show the glomeruli.

What could this mean for kidney patients?

This study will help us to understand FSGS, may lead to diagnostic tools to predict and detect early recurrence and could lead to much needed treatments.

“We want to understand how these antibodies might cause damage in pFSGS so that we can develop new treatments to prevent injury. This new and exciting technology allows us to study the interactions between cells within the human kidney during the early stages of pFSGS.

"With this funding, we hope that our findings will provide an essential foundation for the development of much needed targeted treatments.” Katherine Bull.