Acute rejection remains a major threat to kidney allograft survival despite substantial advances in immunosuppressive therapy. The incidence of acute rejection has markedly declined over the past three decades; however, it continues to contribute significantly to graft dysfunction and loss. The two principal forms of acute rejection are T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is characterized by lymphocytic infiltration and tubular injury, whereas ABMR results from donor-specific antibody–mediated endothelial injury and is associated with microvascular inflammation, C4d deposition, and transplant glomerulopathy. Mixed rejection may also occur and is associated with worse outcomes. ABMR is now recognized as the leading cause of late graft loss, while TCMR remains an important independent risk factor and may precipitate antibody-mediated injury. Diagnosis is based on histopathologic evaluation of kidney allograft biopsy, and treatment depends on the rejection phenotype and severity. Standard therapies include glucocorticoids, antithymocyte globulin, plasmapheresis, and intravenous immunoglobulin. Optimal prevention relies on adequate immunosuppression, medication adherence, and careful donor-recipient matching. Emerging molecular diagnostics and novel targeted therapies may improve future rejection management.
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