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Test could warn of problems for kidney transplant recipients

Assay for biomarker could reduce need for biopsies

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A simple test might reveal whether a kidney transplant recipient is at imminent risk of organ rejection. A study finds that the test, which checks urine levels of an immune protein, might lessen the need for kidney biopsies in some patients and pinpoint others who might safely reduce their dose of immune-suppressing drugs.

Increases in urine levels of the immune protein, called CXCL9, often show up in patients a month before an episode of organ rejection, researchers report August 22 in the American Journal of Transplantation. “That could be pretty useful,” says Kim Solez, a pathologist at the University of Alberta in Edmonton, Canada, who has worked on standards for assessing biopsy data from transplant recipients. In a best-case scenario, screening for CXCL9 and other biomarkers would do no harm and might benefit many patients. “But it depends on how reliable it is,” says Solez, who wasn’t part of the study team.

A kidney biopsy – surgical removal of a small piece of tissue – is the standard procedure for determining if a transplanted organ is in danger. In rejection, the immune system attacks the organ, damaging tissue and posing the risk of kidney failure, meaning that the organ stops filtering blood. Rejection can be gradual or sudden. Doctors can treat rejection with strong immune suppressants, but early symptoms such as fever can be hard to interpret and misleading.  

Doctors resort to biopsies when blood tests or symptoms show signs of rejection. But even when seemingly necessary, many biopsies find that a patient isn’t having an acute rejection episode, says study coauthor Peter Heeger, a transplant nephrologist at Mount Sinai Hospital in New York City. Sometimes the patient’s symptoms come from fighting an infection.

Because of these vagaries, less-invasive and more-accurate tests would ease the burden on patients and improve doctors’ ability to monitor transplants, he says. Toward that end, Heeger and his colleagues evaluated 258 kidney recipients by testing samples of their urine periodically for up to two years after their surgeries.

During the study, 79 patients underwent a biopsy after doctors observed suspicious symptoms or blood readings. Some of these patients were indeed in the throes of kidney rejection, and some weren’t. The still-experimental urine tests revealed that patients with high levels of CXCL9 had a tripled likelihood of rejection compared with those with low readings. Having low CXCL9 levels also indicated better blood filtration in the donor kidney, other tests showed.

Transplant recipients routinely get drugs to suppress their immune systems, but these medicines leave the patient susceptible to infection and some, such as steroids, can cause disagreeable side effects. With further testing, Heeger says, the urine test might identify patients who have low CXCL9 levels and thus might require less immune suppression since they would have a lower rejection risk.

Editor's Note: This story was updated on September 10, 2013 to correct the number of patients in the study who underwent biopsies.

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