A new test could help stop kidney transplant rejection. (AP Photo/Ebrahim Noroozi)
Researchers have developed a new urine test that allows doctors to diagnose and predict acute rejection of transplanted kidneys more quickly and accurately than current standard tests, potentially saving the U.S. millions of dollars in health care costs annually.
The test, named QSant, was developed by researchers at NephroSant, a spinout company of the University of California, San Francisco specializing in kidney health technology. A patent application for the test, which is expected to launch at select clinics in the coming weeks, was published by the World Intellectual Property Organization on March 11.
"There is no other urine test that detects kidney transplant rejection," Minnie Sarwal said in an interview with The Academic Times. Sarwal is the founder and CEO of NephroSant and a professor in residence of surgery at UCSF. "To my knowledge, there is nothing else out there for the type of information we get from this test."
According to the National Institutes of Health, more than 661,000 Americans suffer from kidney failure. Of these, 468,000 live on dialysis, while the other roughly 193,000 people live with a transplant. However, even patients who have had their kidney transplant for many years are at risk of rejection, which can be fatal if not treated quickly.
"A transplant is a treatment, not a cure, and is sustained by immunosuppression for life," Sarwal said. "It's just, your risk stratification changes with time."
Chronic kidney disease is a tremendous strain on patients' health and also a huge source of health care spending. Though patients with kidney failure only account for 1% of the population on Medicare, they account for 7% of its spending. This figure only increases when considering kidney damage that has not progressed to failure.
"By the time we detect damage or injury, the burden to the health care system is actually enormous," Sarwal said in a NephroSant video. "28% of the Medicare spend is actually spent on managing kidney damage and kidney failure. Anything that can eliminate or minimize that burden is likely to have a massive impact on the economic health of any country."
Though it never goes away, the risk of rejection is highest in the months immediately following a transplant procedure. Yet, as long as the original donated kidney was determined to be a suitable match for the recipient through blood and tissue testing, even acute rejection can be reversible if detected soon enough.
However, kidney rejection is generally detected through large jumps in the results of regular blood tests, which are then followed up by an invasive biopsy. This results in the loss of precious time in diagnosing and treating rejection, as well as several additional clinic visits.
Sarwal and her colleagues addressed this problem by focusing on urine, a fluid more directly associated with the kidneys than blood, and one that is accessible without any medical procedure.
"Blood, that's really a distal biofluid. It's also reflecting what's happening in the rest of your body," Sarwal said in the video. "So to try and pick up something that's specific to the kidney, the signal is actually a lot more diluted. The signal of what we're picking up of these markers in the urine is actually a highly amplified signal."
In addition to being highly accurate, the new test is also completely noninvasive, eliminating the need for a patient's blood to be drawn. Patients collect their own samples using a kit containing a preservative, eliminating the need for any needles or additional clinic visits, which is especially important for patients undergoing immunosuppression treatments during the COVID-19 pandemic.
After the patient sends a sample to the lab, it is tested for a series of biomarkers in the urine. The results are then run through an artificial intelligence algorithm to assign the patient a "Q score," an overall measure of the degree of kidney injury and likelihood of acute rejection. Unlike other tests for kidney rejection, the Q score is on a sliding scale rather than a simple positive or negative reading.
"It's not binary. The greater the score, the greater the injury, over the threshold of 32," Sarwal told The Academic Times, referring to the threshold Q score for acute kidney rejection.
Sarwal and her team evaluated their test in a 2020 study in Science Translational Medicine in which they used it on a cohort of 601 samples from transplant patients. They found that the test predicted acute rejection with an accuracy of 96%. Another study on a smaller cohort of 223 samples found an accuracy of 98.2%.
While the patent for this testing method is pending, the invention has already been slotted for production by NephroSant for as soon as this month, where it will be deployed in various transplant clinics across the country. However, Sarwal hopes that in the coming years the test will become even more widely used. She and her team are also working on adjusting their algorithms to assess kidney injury after exposure to COVID-19.
"It bothers me that we pick up their organ system perturbation so late that we miss rejection until really it's like a wildfire in that kidney," she said in the video. "By the time we treat it, we can't really bring the kidney back to its original state of health. I've been doing this because I believe I can do better."
The application for the patent, "Noninvasive Method to Quantify Kidney Function and Functional Decline," was filed Sept. 4, 2020, to the World Intellectual Property Organization. It was published March 11, 2021 with the application number WO2021046339. The earliest priority date was Sept. 5, 2019. The inventors of the pending patent are Minnie M. Sarwal and Joshua Y. Yang, University of California, San Francisco. The assignee is the Regents of the University of California.
The Academic Times