By Merritt McKinney

NEW YORK, Mar 28 (Reuters Health) - A newly developed urine test may one day reduce the need for the sometimes painful biopsies used to diagnose organ rejection in kidney-transplant recipients.

In a small study, the test, which measures levels of two genes linked to kidney-transplant rejection, identified about four out of every five cases of acute kidney rejection.

After having a kidney transplant, patients must take immune-suppressing drugs for life to keep the body from rejecting the new organ. Still, rejection of transplanted kidneys remains a serious problem, affecting about 35% of all recipients during the first year after transplantation.

The standard method of diagnosing acute kidney rejection is a biopsy, during which a fine needle is used to remove samples of kidney tissue, which are then analyzed under a microscope. Biopsies can be painful, and may cause complications, including blood in the urine, blood clots, shock and kidney failure.

To develop a test for kidney rejection that would cause fewer complications, Dr. Manikkam Suthanthiran, of Weill Medical College of Cornell University in New York, and colleagues focused on two proteins involved in the body's immune response to outside invaders.

One of the proteins, perforin, is thought to drill holes in cells that are under attack by the immune system (kidney cells in this case). Then, the other protein, granzyme B, passes through these pores and attacks the cells' genetic material.

Suthanthiran and a colleague at Cornell, Dr. Baogui Li, developed a test that measured urine levels of the two proteins' genetic material RNA, which is formed when a gene is activated or expressed. The researchers suspected that high levels of perforin and granzyme B RNA in the urine would be a sign that the kidney was in distress, Suthanthiran told Reuters Health in an interview.

In the study, urine levels of the proteins' genetic material were indeed higher in 22 transplant recipients who had biopsy-confirmed kidney rejection than in 63 patients whose kidneys had not been rejected. Using predetermined cutoffs for perforin and granzyme B RNA levels, the researchers were able to identify about 80% of all cases of acute rejection, according to the report in the March 29th issue of The New England Journal of Medicine.

The test is "a noninvasive replacement for the biopsy procedure," Suthanthiran told Reuters Health.

But several questions remain to be answered before the test will be used to diagnose acute kidney rejection, according to an editorial that accompanies the study.

"How useful these new tests will prove to be and how often they will be used for the diagnosis of rejection depend on several factors," states Dr. Jean-Paul Soulillou of Hotel Dieu in Nantes, France.

Soulillou points out that the test missed one out of every five cases of rejection and that the rate of false-negative results has not been studied extensively. He also notes that the feasibility and cost of measuring the perforin and granzyme B RNA remains to be seen.

According to Soulillou, the test may turn out to be most useful not for diagnosing cases of acute rejection, which have been on the decline, but for detecting more gradual changes in the immune system's response to transplanted kidneys.

In the interview, Suthanthiran also mentioned this other role for the urine test. Right now, doctors diagnose kidney rejection "after the fact," he said. If a patient has a problem, then the physician looks for the source of the problem, he explained. But regular urine testing may identify patients who are at risk of going into rejection, Suthanthiran said.

In the study, levels of perforin and granzyme B RNA 4 to 9 days after transplantation were higher in patients who went on to develop acute rejection.

Despite the encouraging results of the study, Suthanthiran cautioned that the findings need to be confirmed in larger studies that include patients from more than one transplant center. He noted that the National Institutes of Health is funding several such ongoing trials.

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