Could a new blood test identify rejection earlier in kidney transplant patients?
Mr George Nita is a surgeon and researcher from the Royal Liverpool University Hospital, and doctoral candidate in bioinformatics at the University of Liverpool. He received the Kidney Research UK and Stoneygate funded Professor Michael Nicholson transplant surgeon doctoral fellowship award of £90,000 to look at whether a new type of blood test can identify kidney transplant rejection early.
The problem
Rejection is when the body's immune system recognises a transplanted kidney as ‘foreign’ and attacks it. During the first year after a kidney transplant, up to 20% of patients will experience rejection, which can damage the donated kidney. One in five patients will lose their transplanted kidney and return to dialysis within five years of receiving the new kidney.
One of the causes of rejection is antibodies – proteins normally made by our immune system to protect the body from infection – targeting the transplanted kidney.
Transplant patients are monitored for signs of rejection mainly by identifying a decline in the new kidneys function. As there may not be any symptoms, monitoring is based on a marker called creatinine in the blood. Rejection is then investigated with a blood test for antibodies and may require a biopsy to confirm a diagnosis. A biopsy is invasive, requires hospital admission and carries some risk, and by the time a diagnosis is reached antibodies may have already damaged the transplanted kidney. Therefore, there is a need for non-invasive tests to identify rejection promptly and enable earlier treatment.
The solution
When cells of the transplanted kidney are damaged during rejection, they release their contents, including tiny pieces of DNA, into the bloodstream. George will see if a blood test for this DNA can detect this, before the currently used change in creatinine levels.
George will also look at whether a more personalised approach to post-transplant monitoring and medications could be informed by using artificial intelligence (AI). He will develop a model to try and predict a patient’s likelihood of developing rejection, based on different risk factors.
George will also look at how older age impacts the risk of antibody formation and rejection, and whether immunosuppression could be tailored better to this patient group in the future, aiming to reduce the risk of taking high doses of immunosuppression medications.
What does this mean for kidney patients?
Developing a test which could identify antibody mediated rejection of a kidney transplant earlier could mean earlier interventions in the future to help protect the kidneys from damage, and in some cases eliminate the need for biopsies which carry some risk.
Meet the researcher
“The focus of this project was led by kidney patients, whose priority in this area was research to prevent rejection and make kidneys last longer.
“I often see transplant patients come in with a rise in creatinine. We do routine tests, imaging, test for antibodies and book the next available biopsy, which can be days away. The turnaround for results is approximately two to three weeks – and this is when the sample obtained is good enough to make a diagnosis. Meanwhile, we are sometimes forced to treat the patient with steroids without being sure if rejection is happening, in an attempt to protect the kidney. Antibody-mediated rejection also requires a treatment that is quite different and more advanced, with plasma exchange and intravenous immunoglobulins for example. I wouldn’t want this current approach if I was treating my mum, so why should we for our patients? We must do better, and we need better testing to accurately identify rejection earlier!
“It is amazing how much and with what pace science and technology has advanced in transplantation surgery and immunology. 10-15 years ago, a lot of things seemed like science fiction but are now rapidly emerging as feasible techniques allowing more suitable transplants, improving the quality of organs and the available treatment afterwards. I am grateful to Kidney Research UK and the kidney community for supporting this research to try and bring new technology to the bedside.” Mr George Nita MBChB MSc MRCS
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