Looking for new markers of kidney rejection in children to support personalised care

03 March 2023

The problem

Although dialysis is an important treatment for kidney failure, the best long-term approach is a kidney transplant. After a kidney is transplanted, rejection may occur. This happens because the immune system of the patient recognises the new kidney as foreign and attacks it, potentially leading to the loss of the new organ. Currently, medicines designed to suppress the immune system are the best way to reduce the risk of rejection. While these drugs often offer good protection for the new kidney, they also decrease how well a child can respond to bacteria and viruses, making infections more frequent and potentially more severe.

Routine screening to detect the early signs of kidney rejection involves blood tests, including measurement of a chemical called ‘creatinine’. The earlier increases in creatinine are detected, the better the patient outcomes. However, there may be irreversible damage to the transplanted kidney by the time the increased creatinine is detected. If increases in creatinine are found, a biopsy (surgery to remove and test a very small piece of the kidney) may be needed to check the health of the kidney if no identified cause can be found in other tests (such as exclusion of infection and blockage). This approach is invasive, requiring an anaesthetic, and may miss changes in other parts of the kidney. There is an unmet need to develop new less invasive and more accurate ways to monitor the early signs of kidney rejection.

The solution

Professor Stephen Marks from University College London Great Ormond Street Institute of Child Health will employ a research student to look for new ways of identifying kidney rejection before it happens. These signs, known as ‘biomarkers’, are expected to rely on specialised blood tests, offering a simpler and safer approach than biopsies.

Professor Marks will look at RNA (the cell’s instructions for making proteins) from immune cells of paediatric kidney transplant recipients with organ rejection. By comparing this information with medical records, the team will look for patterns and ways of predicting when rejection will occur. They will then compare these results to traditional measures such as urine, blood and biopsies. Finally, the team will check the ability of the developed biomarker to predict kidney rejection in patients.

Professor Stephen Marks

“I am honoured and thrilled to be the recipient of the Laurence Isaacson Award which we will use to improve the lives of children and young people who have irreversible kidney failure requiring kidney transplantation. The public perception is that kidney transplantation is a cure, but they have a limited lifespan and children and young people usually require more than one kidney transplant during their lives. This award will help us identify better ways of detecting kidney injury which hopefully means we could treat rejection earlier and makes these kidney transplants last longer.” Professor Marks

What this might mean for kidney patients

By developing a new biomarker test that allows early signs of rejection to be identified promptly and in non-invasive way, we could transform the management of children with kidney transplant. This approach would allow easier and more precise monitoring of patients, supporting healthcare providers in decisions on personalised medicines - how much, and what type, of immunosuppressive medicines are needed.