Urine Test Helps Detect Kidney Transplant Rejection

Twenty percent of patients experience kidney transplant rejection even after a long waiting time till 6years. The recipient's immune cells recognize the newly received kidney as a foreign organ and thus on refusing the acceptance of the donor's antigens, results in transplant rejection.

The methods utilized to test for kidney rejection at present includes invasive biopsy procedures, (that requires multiple days of hospitalization and risks of complications) or creatinine blood tests (do not always yield definitive results). Moreover 70-80 percent of biopsies end up being normal.

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‘New easier, non-invasive alternative to traditional methods utilized for testing kidney transplant rejection – using exosomes (tiny vesicles containing mRNA) from urine samples of patients undergoing a biopsy, provides a group of 15 genes that were able to distinguish between normal kidney function and rejection. This assessment of transplant rejection on patients with stable kidney function may help discover similar signatures to detect subclinical kidney transplant rejection in the future.’

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To overcome these hurdles, a new easier alternate way that is noninvasive to test for transplant rejection using exosomes – tiny vesicles containing mRNA – from urine samples, was proposed by a study at Brigham and Women's Hospital and Exosome Diagnostics, published in the Journal of the American Society of Nephrology.

Exosomes are extracellular vesicles of a cell that contains protein, DNA, and RNA of the cells that are involved in secreting them and are capable of affecting cell function and behaviour.

"Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops. If the rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges." "These findings demonstrate that exosomes isolated from urine samples may be a viable biomarker for kidney transplant rejection," says Jamil Azzi, MD, associate physician in the Division of Renal Transplant at the Brigham and an associate professor of Medicine at Harvard Medical School.

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Exosomes in Kidney Transplant Rejection

The study team analyzed the urine samples from 175 patients (who were already undergoing kidney biopsies) for isolated urinary exosomes from the immune cells of the newly transplanted kidneys, rather than following prior attempts of characterizing ordinary urine cells. The protein and mRNA were isolated from these vesicles and observed for a rejection signature.

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The degradation of mRNA is protected by the exosomal vesicle, thereby allowing the genes within the mRNA to be examined for the match rejection signature. It was found that a group of 15 genes were able to distinguish between normal kidney function and rejection.

Also, the team had identified five genes that could specifically distinguish between two types of rejection: cellular rejection and antibody-mediated rejection. As the mRNA tends to decay very quickly without the protection of extracellular vesicles outside, it makes it difficult to perform the test in a clinical setting.

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Since the test was done on patients undergoing an already suspected biopsy for rejection, the team additionally plans to test this method on patients with stable kidney function and study the same signature to detect subclinical kidney transplant rejection.

"Our paper shows that if you take urine from a patient at different points in time and measure mRNA from inside microvesicles, you get the same signature over time, allowing you to assess whether or not the transplant is being rejected. Without these vesicles, you lose the genetic material after a few hours." "What's most exciting about this study is being able to tell patients who participated that their effort allowed us to develop something that can help more people in the future," says Azzi.

Source-Medindia