The Diagnosis and Grading of Acute Kidney Allograft Rejection: An Overview
Rapid catastrophic rejection of the transplanted kidney within minutes or the first few hours after transplantation is called hyperacute rejection. The term accelerated rejection has been used to categorize episodes of renal dysfunction occurring during the first several days after transplantation. Hyperacute and accelerated acute rejection begin with injury to the endothelium of the arterial and capillary compartments of the renal parenchyma. This type of rejection is a result of recipient pre-sensitization to donor-incompatible blood groups or HLA antigens. Such sensitization typically occurs because of prior transplantation, blood transfusions, or pregnancies. The endothelial injury leads to a complex cascade of events involving complement activation, and results in vascular thrombosis and ischemic necrosis of the allograft within a few hours or days after transplantation.
Acute rejection developing after the first 5-7 post-transplant days is generally a manifestation of cell-mediated immune injury. It is believed that both delayed hypersensitivity and cytotoxicity mechanisms are involved. The immune injury is directed against HLA, and possibly other cell-specific antigens expressed by the tubular epithelium and vascular endothelium. The expression of Class I and Class II HLA antigens on these cells can be readily demonstrated by immunoperoxidase studies performed on renal allograft biopsies. Immunophenotypic characterization of lymphocyte populations in-situ has generated conflicting data, with various authors reporting the predominance of CD4-positive cells, CD8-positive cells, or macrophages. It is likely that these differences are due to differences in patient selection, or to sampling of tissue at different stages in the evolution of the alloimmune response.
In the Banff Schema for renal allograft pathology, acute rejection is recognized by the presence of tubulitis and intimal arteritis. Tubulitis is defined as infiltration of the tubular epithelium by leucocytes, usually lymphocytes. Infiltration of the arterial intima is referred to as intimal arteritis. The intensity of the infiltrate, and the severity of tubulitis and intimal arteritis are used to classify rejection into mild, moderate, and severe acute rejection categories. Such a grading system is a useful way of indicating how urgently and intensively a particular episode of rejection needs to be treated. Biopsies with histopathological alterations insufficient for a firm diagnosis of rejection are said to show borderline changes. Decisions regarding whether or not such cases are to be treated should be based on clinical considerations.
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