Personalising treatments for focal and segmental glomerulosclerosis patients receiving a kidney transplant
Professor Alan Salama from University College London has received a Kidney Research UK and Stoneygate funded Professor Michael Nicholson research project grant of £210,000 to look at developing a new test to detect the presence of harmful proteins or other compounds (known as factors) to the kidneys in focal and segmental glomerulosclerosis patients to understand the causes better and which treatments may be most effective, with the aim of preventing recurrent disease in the new transplant.
Focal and segmental glomerulosclerosis patients have a higher risk of transplant loss
Primary focal and segmental glomerulosclerosis (FSGS) is a rare disease which causes damage to the glomeruli (the tiny filters in the kidney). Damage to these tiny filters leads to them being replaced with scar tissue, stopping them from working properly. In just under half of the patients with primary FSGS, renal replacement therapy such as dialysis or a kidney transplant will be necessary.
For FSGS patients who undergo a kidney transplant, disease returns in around a third, often within hours of a transplant. In around 40% of these patients their transplant is lost early. For some patients, the disease can return after several different transplants, leading to a permanent return to dialysis.
Meet Professor Alan Salama
Professor Alan Salama is a consultant in kidney medicine at University College London and the Royal Free Hospital specialising in kidney diseases involving the immune system.
This Michael Nicholson research project grant will mean Alan and his team can develop and validate this new test to try and detect and identify harmful factors in the blood of FSGS patients.
Harmful factors in the blood in focal and segmental glomerulosclerosis
It is thought there is a factor present in FSGS patients’ blood which causes damage to the kidneys. We know that different patients have different causes of their FSGS, some of which can be treated by using specific therapies, but for many patients there is no effective treatment.
Alan will use kidney cells grown in their lab, making an artificial glomerulus, to which blood samples from patients with FSGS will be added (some of which will be from the NURTuRE biobank). Protein would not usually pass through the glomerular filters, however if they are damaged it will, indicating the presence of one of the harmful FSGS factors in the blood.
If a harmful factor is present, the blood will be further tested to determine what sort of factor it is, specifically whether this is an antibody, proteins made by the immune system shown to damage the kidneys in some cases of FSGS, or something else. If antibodies are causing a patients’ FSGS, this can be treated with specific targeted therapies which stop antibody production.
Protecting kidney transplants in focal and segmental glomerulosclerosis patients
A blood test to identify the presence and type of one of the harmful factors in the blood of FSGS patients, could be used in the future to screen these patients before transplant surgery. This could allow doctors to try and remove this factor from the blood to protect the transplanted kidney, helping it stay healthier for longer.
“At the moment our understanding of what causes FSGS and the treatments we have are limited. Developing this test could mean we have new approaches that meet the needs of individual patients in the future, identifying who might relapse and who might not, and understanding which therapies might be best in each case.
“Using NURTuRE, which includes 49 FSGS patients who’ve had a transplant, with linked clinical data, enables us to use a large number of samples to validate our clinical set-up.” Professor Alan Salama
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