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By Amanda Pedersen

Senior Staff Writer

Organ transplant recipients currently face frequent biopsies to monitor for problems like graft injury or rejection, and doctors don't have a good way of differentiating between rejection and other causes of dysfunction. A new blood test is now available, however, that is designed to address both issues for kidney transplant recipients.

Transplant Genomics (Brookline, Massachusetts) launched its first product, the TruGraf blood test, this week at the American Transplant Congress (ATC) meeting in Philadelphia. The TruGraf test is designed to help clinicians identify kidney transplant rejection early and to differentiate clinical rejection from other causes of organ dysfunction. Knowing the true cause of dysfunction makes a difference in treatment options, said Stan Rose, the company's president/CEO who also happens to be a kidney transplant recipient himself.

"The goal is to enable personalized therapy, because every individual reacts differently to [immunosuppressive] drugs and it's really hard to know what's going on without having some kind of molecular indication," Rose told Medical Device Daily.

The company said it will provide the test through a CLIA lab, but the initial availability will be through an early access program with select transplant centers in the U.S. and Europe. "We are commercializing the test in a disciplined way, we think this is the right way to launch," Rose said.

Also at ATC, researchers presented two different studies aimed at validating Transplant Genomics' technology.

While it is important to help physicians differentiate between rejection and other causes of organ dysfunction, Sunil Kurian, a staff scientist at the Scripps Research Institute (La Jolla, California) in the Department of Molecular and Experimental Medicine, and a scientific advisor to Transplant Genomics, said an even more pressing problem in transplantation is subclinical acute rejection, which is simply acute rejection that is detected really early.

"The problem is, unless you do a biopsy, you have no clue what's going on in the tissue and there is no indication of any damage unless you see a rise in creatinine," Kurian told MDD. "But creatinine is kind of a lagging indicator, by the time your creatinine goes up to warrant a tissue biopsy, most of the damage is done."

So the primary goal of the research, he said, is to find a way to catch rejection early on. To date, most studies that have been done on subclinical acute rejection have relied on protocol biopsies, but Kurian said only about 40% of transplant centers do protocol biopsies at three to six months.

Kurian and his fellow-researchers set out to find a signature that could be used to detect subclinical acute rejection early on from a blood draw. The team started with a discovery cohort of 124 samples (33 showed subclinical acute rejection, 31 showed clinical acute rejection, and 60 were considered transplant-excellent patients that did not show signs of rejection). The researchers used Affymetrix' (Santa Clara, California) HT 133 PM Plus Arrays to profile all 124 samples. Then the researchers developed a numerical score to classify the severity of the rejection.

"It's nice to give a clinician a black and white report saying 'yeah, the patient has clinical acute rejection or subclinical acute rejection,' but we thought it's even better if you give them more granular information in terms of the severity of disease," Kurian said. "Basically we showed molecular scores that clearly separate these three classes so not only would you get a prediction saying that the patient belongs to a certain phenotype, but it tells you 'here is clinical acute rejection with a score of 100' or something, so the doctors can actually relate to that score and treat the patient accordingly. That was one of the goals."

According to John Friedewald from Northwestern University's Feinberg School of Medicine (Chicago) and the lead author on the study, the research validates the first blood-based signature for subclinical acute rejection and demonstrates the value of integrating predictive molecular biomarkers into clinical practice to serially monitor and improve long-term outcomes for kidney transplant patients.

"A noninvasive test for subclinical acute rejection could reduce the need for protocol biopsies, inform the need for a 'for cause' biopsy and help with monitoring and adjustment of therapy," Friedewald said. He is also a transplant nephrologist at Northwestern Memorial Hospital and the Kovler Organ Transplant Center (both Chicago).

For a second study presented at ATC, which Kurian was the lead investigator on, the researchers used the same samples from only the validation cohort of the first study, but this time the samples were profiled using next-generation sequencing (NGS) technology (the Ion Torrent Proton) from Life Technologies (Carlsbad, California). They concluded that gene expression signatures for subclinical acute rejection, clinical acute rejection, and transplant excellence (stable patients) can be detected as robustly with RNA sequencing as with microarrays.

"We couldn't tell microarrays apart from NGS," Kurian said.

Rose said both studies validate the use of Transplant Genomics' tests in both peripheral blood and biopsies to classify the immune status of kidney graft recipients. "The validation of the first blood-based signature for subclinical acute rejection is an important milestone in our efforts to offer noninvasive serial monitoring of immune status in kidney transplant recipients," he added.

Last year, the same group of researchers presented earlier studies at the World Transplant Congress that demonstrated the feasibility of Transplant Genomics' approach. In those studies, peripheral blood gene expression profiling demonstrated "excellent" potential as a non-invasive monitoring tool that could enable differential diagnosis of graft status in kidney and liver transplant recipients, they noted (Medical Device Daily, July 31, 2014). //

Published  May 6, 2015

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