Researchers from Rutgers Health, along with a team of medical scientists engaged in a significant global study, have uncovered new indicators of kidney transplant rejection. These findings could enhance the accuracy of diagnosis and treatment for patients who have undergone kidney transplants.
The study, which appears in The New England Journal of Medicine, involved an examination of over 16,000 kidney transplant biopsies. It became evident that certain results, once considered questionable, actually signify a higher risk of transplant failure.
“This research shows that inflammation in smaller blood vessels surrounding the kidneys can predict future complications,” commented Vikas Dharnidharka, chair of the pediatrics department at Rutgers Robert Wood Johnson Medical School and a co-author of the study.
While kidney transplantation generally offers a better quality of life for patients with nonfunctional kidneys compared to dialysis, many transplants fail due to the immune system’s rejection of the new organ.
To minimize the risk of rejection, doctors prescribe immunosuppressive medications to transplant patients. They monitor the health of the transplanted kidneys through blood tests and biopsies, adjusting medication levels accordingly.
Post-transplant care necessitates a careful balance between shielding the transplanted organ from immune attacks and protecting the patient from infections that can arise from an overly suppressed immune system.
“Using stronger immunosuppression to tackle rejection increases the chance of serious infections,” Dharnidharka warned. “Thus, this decision is far from straightforward, as it involves significant risk.”
The research analyzed kidney biopsies taken between 2004 and 2023 from over 30 transplant centers in Europe and North America. The team applied the most recent guidelines from the Banff Classification, which serves as an international framework for diagnosing transplant rejection, to categorize the biopsy findings.
A central theme of the study revolved around microvascular inflammation, which refers to damage to the small blood vessels in the newly transplanted kidney. The 2022 revision of the Banff Classification introduced two new categories addressing this inflammation type. The first category, labeled “microvascular inflammation/injury, DSA-negative, C4d-negative” (MVI), signifies inflammation absent typical hallmarks of antibody-mediated rejection. The second category, known as “probable antibody-mediated rejection,” denotes milder inflammation with some presence of antibodies.
The researchers set out to determine if these new classifications would yield valuable insights regarding the outcomes for transplant patients. The results were definitively affirmative.
Among the analyzed biopsies, 503 fell into the MVI category, while 285 were classified as probable antibody-mediated rejection. Previous guidelines would have classified these cases as non-rejections, but the latest findings linked them to a heightened rejection risk.
Patients diagnosed with MVI had over double the five-year risk of graft failure compared to those showing no signs of rejection. In contrast, patients with antibody-mediated rejection faced almost three times the likelihood of graft failure when compared to non-rejecting patients.
The study further revealed that patients with these newly defined inflammation types were at an increased risk for more severe rejection or long-term kidney damage.
These outcomes strongly support the diagnostic value of the new classification system and lay the groundwork for future trials aimed at improving care for patients identified in these categories.
“The evidence suggests that we should adjust our treatment strategies for patients fitting these categories,” Dharnidharka stated, who also serves as physician-in-chief at the Bristol-Myers Squibb Children’s Hospital at Robert Wood Johnson University Hospital. “The key questions are what the optimal treatment is and its dosage. It’s essential we conduct tests to analyze various strategies effectively.”
Initial clinical trials investigating diverse treatment approaches for these inflammation types would likely begin with adult patients before being expanded to include pediatric transplant recipients, Dharnidharka noted, emphasizing that kidney failure occurs more frequently in adults, facilitating the recruitment of larger adult patient cohorts for extensive studies.
Looking ahead, the implications of this study’s results may extend beyond kidney transplants, potentially affecting heart, lung, and other organ transplants, where similar inflammatory processes may arise. Approximately 25,000 Americans undergo kidney transplants annually, in addition to 20,000 receiving other organ transplants.
