Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation

Antibody-mediated rejection (AMR) remains a leading cause of kidney allograft failure, posing significant clinical and economic challenges. Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss. The diagnostic criteria and classification of AMR have evolved considerably over the past three decades, driven largely by the Banff classification. The latest Banff 2022 classification introduced two additional subcategories of "microvascular inflammation, donor-specific antibody-negative, C4d-negative" and "probable AMR". Traditionally, graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria, and the invasive biopsies. Noninvasive tools using blood and urine biomarkers, including cellular assays and molecular profiling, are increasingly being investigated. Technologies such as the Molecular Microscope Diagnostic System show promise, with studies reporting 80% sensitivity and 90% specificity in detecting AMR. Treatment of AMR remains inconsistent. Recent advances, including CD38 antibodies, have demonstrated up to 60% efficacy in reversing AMR, while complement inhibition shows potential in severe early cases. Ongoing clinical trials evaluating high-dose intravenous immunoglobulin, efgartigimod, fostamatinib, and other novel therapies aim to expand treatment options. These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.