TY - CHAP M1 - Book, Section TI - Rejection A1 - Bhaskaran, Madhu A2 - Molmenti, Ernesto Pompeo PY - 2023 T2 - Molmenti’s Kidney and Pancreas Transplantation: Operative Techniques and Medical Management, 2e AB - Definition: A recipient’s immune response to foreign antigens expressed by the donor that if unresolved will lead to graft loss. Acute rejection, whether predominantly ascribed to cell-mediated immunity (acute cellular rejection [ACR]) or humoral immunity (acute antibody-mediated rejection [AMR]), often has dramatic and sometimes catastrophic effects on allograft function. In contrast, chronic rejection leads to indolent and progressive loss of allograft function and can be easily missed. Over the last decade focus has gradually shifted more toward AMR due to its recalcitrant and ominous natureIncidence: Acute rejections overall have decreased from over 30% to less than 10% or even 5% in incidence over the last five decades. This is due to widespread use of potent induction agents, careful attention to immunological risks through antibody screening against donor alloantigens, and judicious monitoring of allograft recipientsSignificanceIt is reported that up to 12% of grafts that are lost over 10 years are due to direct consequences of an acute rejection. Acute rejection accounts for another 10% to 30% of graft loss by 10 years after transplantation because progressive chronic injury is linked in many instances to persistent low-level immune injury causing both interstitial fibrosis with tubular atrophy (IFTA) and/or transplant glomerulopathy1Glomerular filtration rate (GFR) can be lower after episode(s) of ACRDecreased GFR leads to increased medical comorbidities and increased risk of deathPatients returning to dialysis have poorer survival than patients who have not undergone transplantation or who have functioning allografts2Types of acute rejection: Classification is based on pathology and concurrent antibody data—Banff Classification (Banff Meeting Reports)3Hyperacute: Rare event due to antibodies targeting human leukocyte antigen (HLA), blood group, and/or other endothelial antigens leading to rapid complement-activated thrombotic microangiopathy with extensive hemorrhage and infarctionCellular: Pathology reflects lymphocyte migration, inflammation, and injury at sites of antigen expression on tubular epithelium and vascular endotheliumBanff 1A: Significant interstitial inflammation (>25% of parenchyma affected, i2 or i3) and foci moderate tubulitis (t2).Banff 1B: Significant interstitial inflammation (>25% of parenchyma affected, i2 or i3) and severe tubulitis (t3)Banff 2A: Mild to moderate arteritis (v1)Banff 2B: Severe arteritis, which is associated with greater than 25% loss of the luminal area (v2)Banff 3: Transmural arteritis, and/or arterial fibrinoid alterations, and necrosis of medial smooth muscle cells occurring in association with lymphocytic inflammation of the vessel (v3)Antibody mediated: Pathology reflects endothelial injury at the site of antibody–antigen interaction. Cardinal features include presence of antibodies in serum of recipients, histologic features such as peritubular capillaritis, vasculitis, glomerulitis, and diffuse presence of C4d on immunostaining in the peritubular capillaries. Even though HLA antibodies are the most implicated, antiendothelial antibodies, monocyte antibodies, major histocompatibility complex class I polypeptide-related sequence A (MICA) antibodies, and angiotensin II receptor antibodies are all potential culpritsMost common sign will be “capillaritis”—leukocytes present in peritubular and glomerular capillariesEvidence of complement activation reflected by staining for C4d in peritubular capillaries (this may be absent in many instances—incidence of C4d negative AMR is still being defined but may be as high as 30% or more)Thrombotic microangiopathy with or without capillaritisIsolated (no tubulointerstitial inflammation) vascular rejection ... SN - PB - McGraw Hill CY - New York, NY Y2 - 2024/03/29 UR - accesssurgery.mhmedical.com/content.aspx?aid=1194187865 ER -