Urine Test Might Predict Kidney Transplant Rejection
WEDNESDAY, July 3 -- An experimental urine test might offer doctors a simple way to tell when a kidney transplant patient is rejecting the donor organ -- or possibly even predict a rejection before it happens, a new study suggests.
Researchers found that a test for three biomarkers in the urine was able to diagnose episodes of what doctors call "acute cellular rejection" among 485 kidney transplant patients. And the same markers seemed capable of spotting patients at high risk of rejection.
Right now, doctors typically diagnose acute cellular rejection only after potential signs and symptoms crop up. And that diagnosis has to be done invasively, by taking a biopsy of kidney tissue.
"Obviously, a noninvasive test would be better," said study leader Dr. Manikkam Suthanthiran, a kidney transplant specialist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, in New York City.
Kidney biopsies are generally safe, although they can involve pain and bleeding. But, Suthanthiran said, biopsies cannot be done on a regular basis to try to catch an episode of kidney rejection early -- before there is damage to the organ.
A urine test, on the other hand, could potentially be used that way.
The new findings, reported in the July 4 issue of the New England Journal of Medicine, are a step in that direction. But the test is not ready for prime time, said Dr. Daniel Rotrosen, of the U.S. National Institute of Allergy and Infectious Diseases, which partially funded the study.
"This approach will require more work to make it useful in clinical practice outside research settings," said Rotrosen, who was not involved in the work.
The study included 485 donor-kidney recipients who had urine samples collected at regular intervals for one year after the transplant. During that year, 220 patients ended up having a kidney biopsy, and 36 were diagnosed with acute cellular rejection.
The researchers found that by measuring three biomarkers in the urine, they were able to distinguish the biopsy-diagnosed episodes of kidney rejection 79 percent of the time.
They also looked at whether the urine test could foretell a kidney rejection, by looking back at urine samples taken in the weeks before patients had a rejection episode. In general, they found that those patients' urine-biomarker levels rose slowly and steadily in the weeks leading up to the rejection, with a sudden sharp rise about 20 days before.
So it's possible, Suthanthiran said, that the test could help spot patients at high risk of rejection. In theory, that would allow doctors to increase a patient's dose of immune-system-suppressing medication -- and hopefully head off an acute rejection episode before there is damage to the donor kidney.
On the other hand, he said, transplant patients whose urinary biomarkers are holding steady might be able to go on a lower dose of anti-rejection medication.
"Our hope is to reduce the immunosuppressive therapy for some patients," Suthanthiran said. That's of major importance, he added, because the immune-system suppression puts patients at increased risk for infections and, in the long term, cancer.
That's the hope, Rotrosen said. More work is needed for it to be the reality.
One question, he said, is whether an even easier test could be developed.
The test in this study measured three specific bits of genetic material called messenger RNA. Messenger RNA carries the information in your genes to the protein-making machinery in your cells -- those proteins are the body's actual workhorses.
Measuring proteins is easier than measuring RNA, Rotrosen said. So research should look at whether testing certain urinary proteins works as well as measuring RNA.
"Proteins are easier to measure through home kits like those that are widely used for pregnancy testing," Rotrosen said.
Suthanthiran said the major question is whether treating patients based on the results of this test does them any good. If you boost a patient's dose of anti-rejection drugs when these urine biomarkers rise, does it ultimately prevent a kidney rejection?
"We need to clearly show that this actually improves patients' outcomes," Suthanthiran said.
Learn more about kidney transplants from the United Network for Organ Sharing.
Posted: July 2013