Landmark Study Unveils New Diagnostic Markers for Kidney Transplant Rejection

Rutgers Health researchers have identified new markers of kidney transplant rejection, offering hope for more accurate diagnoses and improved treatments, potentially transforming transplant outcomes.

An international team of researchers led by Rutgers Health has made a significant breakthrough in understanding kidney transplant rejection, paving the way for more precise diagnosis and improved treatment for transplant recipients. The study, published in The New England Journal of Medicine, analyzed over 16,000 kidney transplant biopsies, revealing new indicators of transplant rejection that had previously been underestimated.

“Inflammation in even the smaller blood vessels around the kidneys predicts trouble down the road,” co-author Vikas Dharnidharka, the chair of pediatrics at Rutgers Robert Wood Johnson Medical School, said in a news release.

The findings are particularly crucial as they highlight the importance of microvascular inflammation — a condition where small blood vessels in the transplanted kidney experience damage. Historically, such inflammation was considered less significant, but the new research underscores its potential role in predicting transplant failure.

Kidney transplants significantly improve the quality of life for patients compared to dialysis. However, they are not without challenges, as the recipient’s immune system can sometimes reject the new organ. To mitigate this, doctors prescribe immunosuppressive medications, balancing the need to protect the transplant from immune attacks with the risk of increasing the patient’s susceptibility to infections.

“If you try to treat a rejection with stronger immunosuppression medicines, you run the risk of life-threatening infections occurring,” added Dharnidharka, who also serves as physician-in-chief of the Bristol-Myers Squibb Children’s Hospital at Robert Wood Johnson University Hospital. “So, it’s not a trivial decision that we make because there is a risk involved.”

The researchers examined biopsies performed between 2004 and 2023 from more than 30 transplant centers across Europe and North America. Using updated criteria from the Banff Classification — a global standard for diagnosing transplant rejection — the study identified two new inflammation categories: microvascular inflammation/injury (MVI) and probable antibody-mediated rejection.

According to Dharnidharka, patients with MVI exhibited more than twice the five-year graft-failure risk compared to those without signs of rejection, while those with probable antibody-mediated rejection were nearly three times as likely to experience graft failure.

“These data indicate that we should be treating patients who fall into these categories differently,” Dharnidharka added, emphasizing the need for further clinical trials to determine the most effective treatment strategies.

The research team believes that the new classification categories could also inform treatment protocols for other organ transplants, including those of the heart and lungs, where similar inflammation might occur.

About 25,000 kidney transplants are performed in the United States annually, with another 20,000 involving other organs. The findings from Rutgers Health’s study offer promising prospects not just for these patients, but also for the broader field of organ transplantation.

Looking ahead, Dharnidharka suggested that clinical trials comparing different treatment approaches for these types of inflammation would likely commence with adult patients before including pediatric cases. This approach is pragmatic given the higher incidence of kidney failure in adults, facilitating the recruitment of participants for robust research studies.

This landmark study not only redefines current understanding of kidney transplant rejection but also sets the stage for future innovations in transplantation medicine, potentially improving the lives of thousands of transplant recipients.