Every year, around five hundred Belgians with kidney failure undergo a kidney transplant. A little under one in three transplant patients 
face rejection. In order to avoid the patient going back on dialysis, signs of rejection need to be picked up very quickly. This is why transplant patients regularly undergo kidney biopsies. The VITO research centre and UZ Leuven, along with three foreign transplantation centres, have identified a non-invasive urine protein biomarker for antibody-mediated rejection (ABMR) following a kidney transplant.

Clinicians' attention has long been focused on T cell-mediated rejection (TCMR), although it is now clear that acute antibody-mediated rejection (ABMR) accounts for almost 50% of the total number of acute rejection episodes in kidney transplant patients. Acute ABMR can lead to chronic ABMR, the incidence of which varies from 5 to 20% within five years of transplantation.

Although the 10-year survival rate remains 65 to 70% for kidney transplantation, this percentage could be far higher if it were possible to intervene more quickly and accurately in the event of ABMR. After all, successful therapy for ABMR is closely linked to a very early diagnosis, which is not a simple matter with the current diagnostic method – the invasive kidney biopsy. At present, routinely recorded biopsies are regularly carried out on transplant patients at pre-determined intervals after the transplantation. It is all the more difficult to increase this necessary number due to the invasive nature of the biopsy. Each biopsy causes a slight injury to the transplant kidney and may lead to further kidney damage.

To lower the number of patients facing fatal ABMR, it is therefore not only necessary to get a better understanding of the major factors that increase the likelihood of rejection and the mechanisms underpinning them but also necessary to develop reliable and non-invasive methods of predicting transplant failures, before the possibility of irreversible kidney damage arises.

Researchers from VITO and the KU Leuven have identified and validated a set of urinary protein biomarkers that can be used to discount ABMR. The protein biomarker urine test allows for a very early diagnosis, gives objective results and is cheap to boot. A set of a maximum of 10 urine proteins can identify patients with and without antibody-mediated rejection. The validation study has demonstrated 99 percent reliability. The margin of false-positive results amounts to 33% thus far, which in the case of a positive result, it will give a definitive result for a kidney biopsy. The number of false-negative results is negligible. When compared to existing parameters, we see that the urine protein markers are quicker and more sensitive at detecting ABMR.

“At the moment, the test can only be carried out at an extra muros specialist laboratory,” explains Inge Mertens from VITO. “The first step we're now taking is towards an ELISA test (Enzyme-Linked Immune Sorbent Assay) that detects the antibodies, so the results can be analysed more quickly at the hospitals themselves. At the same time, we're aiming to develop a point of care test. With an LFA test (lateral flow assay test), patients can now take the test themselves at home, which will allow for far more regular, faster and cheaper testing.”

Making the move from research centre to home testing, however, is not a simple matter. “The niche market for these kinds of tests is small,” explains Inge Mertens. “Moreover, this involves an actually cheap test, which in practice won't cost any more than a COVID-19 test. Similar laboratory tests are sold for thousands of dollars apiece in the US today. The manufacturers don't feel inclined to include a test in their range that – for them – is incredibly cheap.  That's why we're targeting the European manufacturers of diagnostic tests to include this test in their offering as well.” 

The scientific results of the Biomargin project have been published in  Kidney International Reports.


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