Urine Test May Improve Monitoring of Kidney Transplants

Medically Reviewed by Charlotte E. Grayson Mathis, MD
From the WebMD Archives

Mar. 28, 2001 -- A new urine test soon may be able to lower the number of kidney transplants that fail because a person's body rejects them.

The test may promise to replace the unpleasant and sometimes dangerous needles now used to get small samples of a newly transplanted kidney to test for signs that the body is rejecting it. A report in the March 29 issue of The New England Journal of Medicine shows that the test can be just as fast as the needle biopsies and suggests that the test may even be able to predict rejection before it damages the new kidney.

"I think it is a good possibility this will remove the need for transplant biopsy," study leader Manikkam Suthanthiran, MD, tells WebMD. "And it is more than that -- I think it may help us anticipate the rejection."

Similar tests might someday be used to predict rejection of other organs, although urine wouldn't be used; blood samples or even biopsies would still be needed to test organs such as hearts and lungs.

Suthanthiran's study involved 85 kidney transplant patients, 22 of whom were shown by biopsy to be facing rejection. New large-scale studies now are exploring the use of the urine tests to detect rejection in kidney-transplant patients. Other uses for the new type of test will come later if these studies are successful.

Rejection of a transplanted organ occurs when a person's immune system attacks the new organ because it recognizes it as a foreign body. More than one out of three people who get kidney transplants have at least one bout of rejection, which damages or destroys the new organ. Currently, doctors have to perform a series of invasive tests including biopsy in order to diagnose rejection. Because the symptoms of rejection can be subtle, it is easily missed before damage to the transplanted kidney takes place.

The new test looks for very early signs of these unwanted immune-system attacks. These signs are messenger RNA (mRNA) -- or genetic information -- that codes for the killer molecules of the immune system. Sophisticated new techniques can measure the amount of specific kinds of mRNA in a person's urine. Suthanthiran's team now has established cutoff levels for these kinds of mRNA that separate people with rejection of a transplanted kidney from those with other kinds of problems.

The presence of this specific mRNA is one of the first signs that rejection is beginning. So the new tests also could be used to monitor a transplant patient to see whether the immune-suppressing drugs are working right.

"Patients who develop rejection [to their transplants] develop these markers first," says Suthanthiran, chief of transplantation medicine at New York's Weill Cornell Medical Center. "Now we give drugs and say that a patient is immune suppressed -- but we don't really have a good handle on how to measure immune suppression. With this test it may be possible to look and see whether these genes are [present] or not and get a good feel for how much immune suppression a person really is getting."

Christian P. Larsen, MD, PhD, is director of the Emory University transplant center in Atlanta. He did not participate in Suthanthiran's study, but is very familiar with his work.

"I think this test will begin to be incorporated into clinical practice in the near future," Larsen tells WebMD. "It has tremendous potential. It also has the potential to change the way a given patient is managed [by their doctor]. ... [We] may be able to tailor a patient's therapy based on the results [of the urine test]."

But others are not so sure that this sophisticated technique will find wide use. Marcia Wheeler, MS, is a research associate in the urology section of the Yale University Medical School, in New Haven, Conn. She says that mRNA measurement is tricky, and that not all laboratories will get results as good as those reported by Suthanthiran.

"It is difficult to isolate mRNA from urine," Wheeler says. "They say they get 95% success -- the best people get that kind of success, but not everyone. And the isolation of mRNA is really difficult if the urine is infected, and that often is the case in people with kidney rejection."