Levels of certain molecules in the urine of kidney transplant recipients can provide an early sign of transplant rejection, researchers found. The noninvasive urine test could allow doctors to intervene early and protect transplanted kidneys.
After a kidney transplant, patients must take medications with toxic side effects to keep their immune system from attacking the new organ. Even with these medications, about 10-15% of recipients need additional treatment within a year of transplantation.
If signs of kidney injury are detected, doctors typically perform a kidney biopsy. A small piece of kidney tissue is removed to look for rejection-associated damage. Serious complications from a biopsy are rare, but the procedure does carry risks, such as bleeding and pain. In addition, because biopsies are based on small tissue samples, they don’t always give an accurate impression of the overall state of the kidney.
If doctors could track rejection status over time, they could adjust drug doses for more effective treatment. Toward this aim, a research team led by Dr. Manikkam Suthanthiran of Weill Cornell Medical College and Dr. Abraham Shaked of the University of Pennsylvania School of Medicine collected urine samples from nearly 500 kidney transplant recipients. Samples were taken from 3 days to about a year after transplantation. The researchers tested urinary cells for levels of several molecules previously associated with kidney transplant rejection. The study was funded primarily by NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
In the July 4, 2013, issue of the New England Journal of Medicine, the researchers reported that 3 urinary molecules form an effective diagnostic signature for kidney transplant rejection. The signature includes 2 messenger RNA molecules that encode immune system proteins implicated in transplant rejection and an RNA molecule involved in protein production. Levels of these molecular biomarkers distinguished kidney recipients with biopsy-confirmed rejection from those without signs of rejection. The researchers validated the finding in a set of urine samples collected in a separate clinical trial.
To test whether the approach also could predict future rejection, the team analyzed trends in urine samples. Diagnostic signature values for patients who experienced rejection increased slowly but steadily leading up to the rejection and rose sharply about 20 days before biopsy-confirmed rejection. Values for patients with no signs of rejection remained relatively constant. These findings suggest it might be possible to detect and treat impending rejection before substantial kidney damage occurs.
“The test described in this study may lead to better, more personalized care for kidney transplant recipients by reducing the need for biopsies and enabling physicians to tailor immunosuppressive therapy to individual patients,” says study coauthor Dr. Nancy Bridges, chief of NIAID’s transplantation branch.