Issue: April 2021
Disclosures: Bunnapradist reports he has consulted for CareDx and Natera. Gupta reports he is on the scientific advisory board of CareDx. Giullian reports he a member of the board of directors of NephroSant.
April 19, 2021
5 min read
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New surveillance tests can improve survival of donated kidneys

Issue: April 2021
Disclosures: Bunnapradist reports he has consulted for CareDx and Natera. Gupta reports he is on the scientific advisory board of CareDx. Giullian reports he a member of the board of directors of NephroSant.
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The VCU Health Hume-Lee Transplant Center ranked 11th and was among the busiest transplant centers in the United States in 2019, performing 304 kidney transplants.

But Gaurav Gupta, MD, associate professor and medical director of kidney transplantation at VCU, knows transplant programs are not only judged by the volume of transplants performed, but longevity of graft survival during an era of a limited organ supply.

“As you look at the recent history of transplantation, centers have had great success with graft survival – anywhere from 92% to 96% in the first year,” Gupta told Nephrology News & Issues. “But as you look out over several years, in terms of survival, it becomes problematic across the country,” he said. “Graft survival rates go down to about 80% by 5 years and 50% or less, on average, after 10 years.”

Protection of the donated organ

Gaurav Gupta, MD, associate professor and medical director of kidney transplantation at the VCU Health Hume-Lee Transplant Center, said longevity of graft survival is important during an era of a limited organ supply.

Source: Gaurav Gupta, MD

Protecting a scare resource like donated organs is key in efforts to address a wait list of more than 100,000 people. Close to 80% of patients on the list need a kidney and many wait a long time.

The latest data from the Scientific Registry for Transplant Recipients (SRTS) shows “only a quarter of waitlisted patients receive a deceaseddonor kidney transplant within 5 years, and this proportion varies dramatically by donation service area, from 15.5% to 67.8%,” SRTR wrote in its 2021 report.

Likewise, 20% of recovered organs are discarded.

While half of organs transplanted nationally are lost due to patient deaths, others are lost to chronic rejection, many of which are “clinically silent” over time, Gupta said. As creatine clearances begin to worsen, better diagnostic tools – namely, those that can detect earlier that the graft is starting to show signs of rejection – could be helpful.

“Tests that can be more sensitive than serum creatinine and can pick up early rejection of the kidney before significant damage occurs are what we have needed,” Suphamai Bunnapradist, MD, MS, a transplant nephrologist at the University of California Los Angeles, told Nephrology News & Issues.

Non-invasive tests

Suphamai Bunnapradist

Non-invasive tests are now available to help clinicians identify early warning signs of organ dysfunction and ward off rejection (see sidebar). The tests also help the transplant physician develop a more refined mix of immunosuppressive drugs for each patient.

“Generally, transplant centers tend to use immunosuppressive medications in somewhat of a cookie-cutter fashion,” Gupta said. “This involves changing doses but also the same regimen for every patient. We have been searching for the ‘holy grail’ that tells us how much to use for this patient vs. how much to use for others. These new non-invasive tests could help us calibrate immunosuppression better.”

The major advantage of new non-invasive tests is that transplant physicians can now pursue a biopsy to find out if kidney damage has already begun. “It is accurate,” Bunnapradist said, based on his experience using Natera Inc.’s Prospera test in patients who subsequently had a biopsy performed to confirm the result. “I would say we see some indication of damage in 80% to 90% of cases where the blood test had indicated the kidney was in trouble.”

Losing a kidney due to rejection can be a devastating blow to the patient enjoying the freedom and better quality of life as a transplant recipient – and a costly step for Medicare which paid for procuring the organ and the transplant and must now cover the costs for the patient to return to dialysis.

One study showed the average annual Medicare cost for a transplant recipient is $22,000 compared with $47,000 for a patient on dialysis. Those costs increased to $84,000 for patients who had transplant rejection and had to return to dialysis.

Gupta uses CareDx’s AlloSure test. Studies have shown it is effective in detecting signs of graft injury. A new study is underway to determine whether using the test can lead to improved long-term outcomes. Gupta said almost 1,500 patients are involved in the 3-year study, which is expected to end in 2022.

Jeff Giullian

“So far, the results are promising,” Gupta said.

NephroSant is developing a test, called QSant, that uses multiple biomarkers including a proprietary technology for measurement of urine cell-free DNA to detect organ dysfunction.

“We hope that QSant can helps physicians and patients better understand the health of a transplanted kidney, which in turn could help trigger the physician to make the right intervention at the right time to keep the organ healthy as long as possible,” Jeff Giullian, MD, MBA, FASN a transplant nephrologist and chief medical officer for DaVita Inc., told Nephrology News & Issues. DaVita Venture Group recently led a Series A funding round that closed at $16 million to help fund NephroSant’ s test.

Giullian said DaVita was “impressed” with the sensitivity and specificity for humoral and cellular rejection that the test offers.

“Urine can be easy to collect at home or with a clinician, meaning that the QSant test can be readily adapted to a variety of clinical workflows regardless of available staff or site of care,” he said.

Immunosuppressive drug coverage

Both Gupta and Bunnapradist praised the recent vote in Congress to provide lifetime immunosuppressive drug coverage to patients with a kidney transplant.

“A new kidney gives hope of a better quality of life to patients, and by requiring Medicare to cover the critically needed immunosuppressive drugs past 36 months for certain kidney transplant patients, we will help protect that kidney and prevent a return to dialysis,” U.S. Rep. Michael C. Burgess, MD, R-Texas, a member of the House Rules Committee and leader of the House Energy and Commerce Subcommittee on Health, said in a statement after the bill passed the House.

“We hope it can make a difference in protecting precious transplant organs,” Bunnapradist said. “It is an exciting time for us and what these non-invasive tests can show us. The next step is defining which patients can benefit the most and make sure they have the test done early enough for us to detect rejection and reduce damage to the kidney.”

In ranking the need for a kidney transplant, “diabetes and high blood pressure take the first two spots,” Gupta said. “The third reason is re-transplants.

“We need to set a goal of ‘one kidney for life’ so that we can use more kidneys for first timers rather than placing them in patients with a failed kidney ... [T]hat is absolutely, a win-win.”