Researchers at Rutgers Health, in collaboration with an extensive international team, have unveiled critical new insights into kidney transplant rejection that could change the way we diagnose and treat transplant recipients. The findings, published in The New England Journal of Medicine, examined over 16,000 kidney transplant biopsies, revealing that certain previously misunderstood results are significant indicators of increased risk for transplant failure.

“This study demonstrates that even minor inflammation in small blood vessels surrounding the kidneys can forecast potential complications,” stated Vikas Dharnidharka, chair of pediatrics at Rutgers Robert Wood Johnson Medical School and a co-author of the study.
Kidney transplantation generally offers patients a longer, healthier life compared to dialysis, but many transplants ultimately fail due to the body’s immune response rejecting the new organ. To counteract this rejection, physicians prescribe immunosuppressive medications to patients. However, striking the right balance is crucial; these medications help protect the transplanted organ but can also leave patients vulnerable to life-threatening infections if their immune systems are overly suppressed.
“The challenge lies in managing treatment effectively,” Dharnidharka explained. “Increasing immunosuppression can lead to serious infections, making it a complex decision with significant risks.”
This study analyzed kidney biopsies performed from 2004 to 2023 across more than 30 transplant centers in Europe and North America. Researchers utilized the latest criteria from the Banff Classification, which serves as an international standard for diagnosing transplant rejection, to categorize biopsy results.
A primary focus of the research was on microvascular inflammation—damage to the small blood vessels within the transplanted kidney. The 2022 update to the Banff Classification introduced two new categories pertaining to this inflammation. The first, known as “microvascular inflammation/injury, DSA-negative, C4d-negative” (MVI), identifies inflammation without the usual indicators of antibody-mediated rejection. The second category, “probable antibody-mediated rejection,” denotes milder inflammation accompanied by some antibody presence.
The researchers aimed to determine whether these new categories provide actionable insights into transplant patient outcomes. The results were emphatic: they do. Of the 16,293 biopsies analyzed, 503 fell into the MVI category and 285 into the probable antibody-mediated rejection category. Previous classification methods would have categorized these findings as non-rejection, but this latest research links them directly to heightened rejection risk.
Patients exhibiting MVI faced more than double the five-year graft failure risk compared to those without any rejection indicators. Meanwhile, patients with antibody-mediated rejection were nearly three times as likely to encounter graft failure than those with no signs of rejection.
Moreover, the study indicated that patients showing these newly classified types of inflammation were at a greater risk of developing severe rejection or chronic kidney damage over time. These results not only validate the diagnostic potential of the new classification but also lay the groundwork for future clinical trials aimed at enhancing care for these patients.
“These findings suggest we need to tailor treatment for patients identified under these new categories,” Dharnidharka emphasized. “What is the optimal treatment? How much should we administer? We should conduct tests that compare various strategies to find the best outcomes.”
Future clinical trials comparing different treatment methodologies for these types of inflammation will likely prioritize adult patients before extending to pediatric transplant recipients. This focus is due to the higher prevalence of kidney failure in adults, making it simpler to recruit larger groups for significant research projects.
Looking ahead, the implications of this study could extend beyond just kidney transplants; similar types of inflammation may also be relevant for heart, lung, and other organ transplants. Every year, approximately 25,000 Americans undergo kidney transplants, with another 20,000 receiving transplants for other organs.
By refining our understanding of transplant rejection and improving diagnostic capabilities, this groundbreaking research holds the potential to significantly enhance patient outcomes and treatment strategies across various organ transplants.