Analysis of Urinary Exosome RNA Can Diagnose Kidney Transplant Rejection

A panel of mRNA signatures derived from urinary exosomes was shown to be a powerful and noninvasive tool to screen for the body’s rejection of a kidney allograft (a transplant from a genetically non-identical donor).

The traditional biomarkers currently used to monitor a kidney allograft for rejection are late markers of injury and they lack sensitivity and specificity. Allograft biopsies on the other hand, are invasive and costly.

To improve this situation, investigators at Harvard Medical School (Boston, MA, USA) developed a noninvasive clinical test to accurately diagnose kidney allograft rejection. This test was based on the isolation of urinary exosomal mRNAs and the identification of rejection signatures on the basis of differential gene expression.

Exosomes contain the major fraction of mRNA in urine and consequently are an ideal target to probe for molecular biomarkers of kidney diseases. Exosomes are lipid-enclosed extracellular vesicles measuring 30–150 nanometers in diameter that are released by most cells in the body and play an important role in intercellular communication by carrying bioactive molecules (soluble proteins and nucleic acids such as mRNAs) to a target cell. Exosomes in urine are primarily released from renal epithelial cells derived from renal tubular structures and hold promise as one component of a noninvasive liquid biopsy for detecting molecular changes in distinct nephron regions even in the absence of disease. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.

For this study, the investigators isolated exosomes from 175 urine samples obtained from patients who were already undergoing kidney biopsies. The investigators isolated protein and mRNA from these exosomes and identified a 15 gene rejection signature that could distinguish between normal kidney function and rejection. Furthermore, the investigators pinpointed five genes that could differentiate between cellular rejection and antibody-mediated rejection.

"These findings demonstrate that exosomes isolated from urine samples may be a viable biomarker for kidney transplant rejection," said senior author Dr. Jamil Azzi, associate professor of Medicine at Harvard Medical School. "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 rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges."

The urinary exosome study was published in the March 3, 2021, online edition of the Journal of the American Society of Nephrology.

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