Children’s Nephrologists Hope to Use Biomarkers to Better Identify Kidney Transplant Rejection

Dr. Michael E. Seifert is leading a study to evaluate biomarkers for their potential to predict kidney transplant rejection.

A new study at Children’s of Alabama aims to establish a new, non-invasive way to predict kidney rejection through the blood or urine with better accuracy than the current standard.

The study, Biomarkers from Multiple Platforms to Enhance Diagnosis of Rejection in Children and Young Adults after Renal Transplantation (BuMPER-CAR), is led by pediatric nephrologist Michael E. Seifert, M.D. He and the Children’s nephrology team are conducting it using a large biorepository of patients’ blood, urine and kidney biopsy tissue. With this, they’re evaluating individual biomarkers for their potential to predict rejection. They’re also trying to identify a panel of several biomarkers that may be more accurate and may provide results quickly.

“The idea with this study is, hopefully, we can not only find the patients that are having trouble but confirm the patients who are stable, so we can feel confident that we’re not missing something clinically by avoiding a biopsy in that patient.” The results, he said, could be transformative.

An estimated 1,000 children in the U.S. receive a kidney transplant each year—about 15 to 20 of them at Children’s of Alabama. While the procedure is usually successful, 10-15% of patients experience acute rejection each year, and most transplants fail after about 10-15 years. The standard for assessing the health of a transplant has been to measure creatinine blood levels and urine protein levels. If either is elevated, patients must undergo an invasive biopsy, which carries risks of complications—a heavy cost when only about 1 in 5 biopsies show signs of rejection, meaning most are unnecessary.

According to Seifert, one reason for the poor correlation between rejection and creatinine and protein levels is that the tests are “notoriously bad indicators” of transplant health. By the time the creatinine levels signal a problem, the kidney has often already suffered significant injury.

“On the flip side, there are lots of reasons why somebody’s creatinine might become abnormal, or they might start spilling protein in the urine that has nothing to do with rejection. But we must do biopsies to figure that out,” Seifert said. “So, we need better markers to tell us when the creatinine is a problem, so we can make better assessments.”

The study’s genesis came from a nephrology fellow who wanted to do a research project around biomarkers of kidney transplant diseases. A literature search revealed a plethora of “favorite” biomarkers to predict transplant rejection, but Seifert said there was no consensus on which biomarker worked best. “I think that’s part of the reason why, despite having really good data to support their clinical use, a lot of biomarkers remain on the outskirts of clinical medicine and aren’t being integrated into clinical practice,” he said.

The BuMPER-CAR study is funded in part by Natera, a molecular diagnostics company that manufactures a blood test that detects a form of DNA from the donor kidney, called donor-derived, cell-free DNA (dd-cfDNA), that can be a sign of kidney damage. However, the test is approved only for adults and has not been validated in children. One goal of the study is to set baseline levels for children.  

The study also assesses other biomarkers, including new ones in development at Natera and others developed in Seifert’s lab. Researchers hope to see if a panel of any of these biomarkers would perform better than any individual biomarker. They also want to know if the biomarkers can predict the type of rejection, which could help guide management.

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