Urine tests can predict transplanted kidney rejection
Tuesday, April 07, 2020
Two new methodologies offer promise in predicting kidney failure using a simple urine test instead of a biopsy.
University of California, San Francisco researchers say a urine test they have developed would eliminate the need for an invasive biopsy to determine the chances of organ rejection. What's more, monitoring kidney health with a urine sample makes it much easier to identify a problem before the organ suffers irreparable damage.
“Our test can provide a new gold standard of post-transplant monitoring of adults and children,” said senior author Dr. Minnie Sarwal, professor of surgery, medicine and pediatrics at UCSF. The findings appeared in the March 18 issue of Science Translational Medicine.
“The high accuracy of the test can allow a physician to minimize unnecessary invasive biopsies for patients with low risk of rejection, and conversely, triage patients with high risk of rejection for customized immunosuppression. As the test is noninvasive, can be conducted at any time and requires approximately one tablespoon of urine, it lends itself to repeat testing for post-transplant immune monitoring,” Sarwal said.
In the study, a test of 601 urine samples showed better than 95% accuracy in determining rejection risk. The samples came from three transplant centers and represent 332 adult and pediatric patients. One sample was taken just before a biopsy was conducted. A second biopsy-matched sample was taken a week to eight months before a biopsy-confirmed organ rejection. Analysis was done with an assay, which measures cell-free DNA in urine, detects epigenetic changes and levels of four other proteins and metabolites. The combination of these determined whether an organ would be rejected from be stable.
Sarwal said blood determinations of circulating free DNA (cfDNA) require assessing its ratio between the transplanted organ and the overall blood sample in the donor. "Therefore they cannot be used to assess rejection in repeat transplants or multi-organ transplants from different donors. The Q-Score detects rejection in repeat transplants and across a wide range of recipient ages spanning both childhood and adult," Sarwal said.
Georgia Tech and Emory University have developed a test that identifies when the body's immune system starts attacking the organ.
“Before any organ damage can happen, T cells have to produce granzyme B, which is why this is an early detection method,” said Gabe Kwong, a co-principal investigator in the study.
The urine screening uses sensor nanoparticles to identify the enzyme granzyme B. Catching the presence of that enzyme early is important since signs of rejection sometimes don't appear on a biopsy until the organ is damaged.
“This is sensitive enough to possibly detect budding rejection before you see significant injury to the transplanted organ and that could help clinicians treat early to prevent damage,” said Dr. Andrew Adams, co-principal investigator. “Right now, most tests are aimed at organ dysfunction, and sometimes they don’t signal there is a problem until organ function is below 50 percent.”
This study was published in Nature Biomedical Engineering.
“This method could be adapted to tease out multiple problems like rejection, infection or injury to the transplanted organ,” Adams said. “The treatments for all of those are different, so we could select the proper treatment or combination of treatments and also use the test to measure how effective treatment is.”
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