SAN DIEGO — Kidney transplant patients who move into the newly recognized microvascular inflammation category under the revised definition have a moderate risk of poor allograft outcomes, a large study shows. Ta.
Researchers looked at two categories added in 2022 to the Banff Classification of Renal Allograft Pathology, the benchmark diagnostic framework for allograft rejection in kidney transplants, in a study of more than 6,700 kidney transplant recipients. Outcomes were investigated.
In the first category, microvascular inflammation or injury without evidence of donor-specific antibody-mediated responses, graft loss was 2.1 times more likely than in patients without biopsy evidence of rejection (95 % CI 1.5-3.1).
According to Aurélie Sagnier, MD, of the Paris Transplant and Organ Institute, this indicates an “intermediate prognosis” in which patients with antibody-mediated rejection are 2.7 times more likely to experience graft loss (95% CI 2.2-3.3). It is said that there is. Regeneration, reported at the American Society of Nephrology Kidney Weekly Meeting.
The second category (mild microvascular inflammation in which antibody-mediated rejection by donor-specific antibodies is likely, but C4d is not present as a marker of antibody-mediated allograft damage) is associated with long-term graft The risk of failure was higher. The hazard ratio after 5 years after biopsy was 1.7 (95% CI 0.8-3.5) compared with patients without rejection and 1.3 (95% CI 0.8-2.1) before that.
Both of these new microvascular inflammatory phenotype groups were at increased risk for progression of transplant glomerulopathy compared with the absence of microvascular inflammation.
“We believe that recognition of these phenotypes will improve risk stratification and support a more individualized management of kidney transplant patients. We also believe that the differences observed in allogeneic transplant outcomes “Our findings suggest that another mechanism may contribute to the pathogenesis of isolated microvascular inflammation,” said Sagnier.
The results of this study were simultaneously published in a journal. New England Medical Journal.
Antibodies against donor tissue are an important factor in kidney allograft failure, and allograft microvascular inflammation is the “characteristic histological lesion” in these cases. The 2019 Banff classification focused solely on microvascular inflammation in the context of antibody-mediated rejection.
However, graft microvascular inflammation without such circulating donor-specific anti-HLA antibodies is common. “This heterogeneous presentation poses a major clinical challenge, as current treatment strategies are often ineffective, hindering improvements in allograft outcomes and patient care,” Sagnier et al. I'm writing.
The study included 16,293 kidney transplant biopsy specimens taken from 6,798 patients treated at more than 30 transplant centers in Europe and North America from 2004 to 2023. Median follow-up after kidney transplant biopsy was 5.0 years. Graft loss occurred in 490 patients (11.2%).
Of the 788 patients found by the researchers to have one of the newly described microvascular inflammation categories (3.1% antibody negative, 1.7% likely antibody-mediated rejection), 641 The person had previously been classified as having no evidence of rejection.
“These diagnostic modifications are being incorporated into routine practice around the world and will likely have a major impact on therapeutic decision-making and patient care,” the researchers wrote.
Differences in allograft outcomes between groups “suggest that another mechanism may be responsible for isolated microvascular inflammation,” possibly due to innate immunity triggered by natural killer cells and T cells. The researchers suggested that it was a reaction.
“Thus, while the use of antibody-targeted therapy may be considered for isolated microvascular inflammation, the therapeutic response may be limited, as this does not target innate immune mechanisms and T cell-mediated responses. “This suggests the need for potentially effective therapies,” the researchers wrote.
Furthermore, solid organ transplants may be more broadly relevant, as microvascular inflammation is also an important diagnostic feature of antibody-mediated rejection against their allografts, but the clinical phenotype remains insufficient in diagnostic criteria. Sannier et al.'s group pointed out that
“From a prognostic perspective, the identification of these phenotypes could improve the stratification of heart, lung, and liver transplant recipients who are at risk for alloimmune-related disease progression and poor transplant outcomes. “This will parallel observations in renal allograft recipients. The current study has significant implications for therapeutic decision-making and patient care,” they added. .
Of the biopsies they studied that fell into the new category defined by renal transplant rejection, most (57% to 63%) were obtained for clinical indications for biopsy, with Median duration was approximately 11 months.
Recipient, donor, and transplant characteristics are generally similar among patients initially diagnosed with antibody-mediated rejection, those with possible antibody-mediated rejection, or those with no evidence of rejection. Ta. In the no-rejection group, the number of patients with circulating donor-specific antibodies at the time of transplantation was lower than in the antibody-mediated rejection and potential antibody-mediated rejection groups (13.9%, 60.8%, and 74.8%, respectively). .
Limitations of this study include the lack of a standardized immunosuppressive regimen and the lack of consistently recorded data on what regimen was used to assess the association between transplant outcome and treatment. I couldn't do it.
“Furthermore, surveillance biopsies were not systematically performed 1 year after transplantation, so we were unable to fully assess the natural evolution of the microvascular inflammatory phenotype,” the researchers acknowledged. “However, our analysis integrated biopsies performed for clinical indications and provided valuable insight into disease progression.”
disclosure
This research was supported by the nonprofit organization OrganX.
Mr. Sagnier did not disclose any relevant relationships with the industry.
primary source
New England Medical Journal
Source reference: Sablik M et al. “Microvascular inflammation and clinical outcome in kidney allografts” N Engl J Med 2024; DOI: 10.1056/NEJMoa2408835.
