Question:

A 57-year-old woman with autosomal dominant polycystic kidney disease develops end-stage renal disease and undergoes deceased-donor kidney transplantation. During the operation, the surgeon notices that the graft becomes cyanotic and mottled soon after its blood vessels are connected with those of the recipient. Blood flow to the graft ceases, and no urine is produced. Which of the following best explains the findings observed by the surgeon?

Activation of recipient T lymphocytes

Antibody recognition of graft HLA components

Degranulation of recipient mast cells and basophils

Donor T lymphocyte–mediated vasculopathy

Severe renal graft atherosclerosis

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Transplant rejection reactions
Type of rejection	Onset time	Etiology	Morphology
Hyperacute	Minutes to hours	Preformed recipient antibodies against graft antigens	Gross mottling & cyanosis Arterial fibrinoid necrosis & capillary thrombotic occlusion
Acute	Usually <6 months	Exposure to donor antigens induces activation of naive immune cells Predominantly cell-mediated	Cellular: lymphocytic interstitial infiltrate & endotheliitis Humoral: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Chronic	Months to years	Chronic low-grade immune response refractory to immunosuppression Mixed cell-mediated and humoral	Vascular wall thickening & luminal narrowing Interstitial fibrosis & parenchymal atrophy

This patient is experiencing hyperacute rejection of a renal transplant. Hyperacute rejection is an antibody-mediated reaction (ie, type II hypersensitivity) caused by preformed IgG antibodies in the recipient that are directed against donor antigens. These are commonly anti-HLA antibodies (eg, formed during prior blood transfusion or pregnancy) or ABO blood group antibodies.

Hyperacute rejection is usually diagnosed in the operating room when the kidney becomes cyanotic and mottled after anastomosis of the donor and recipient blood vessels. Perfusion through the transplanted organ ceases immediately due to antibody- and complement-mediated vascular injury with subsequent thrombotic occlusion. This rapidly leads to ischemic necrosis of the glomeruli and renal cortex with little to no urine output and irreversible graft loss.

To minimize the risk of hyperacute rejection, donor and recipient ABO and HLA cross-matching is performed prior to renal transplantation.

(Choice A) Activation of recipient T lymphocytes is the primary mechanism of acute organ transplant rejection. Recipient T cells are sensitized by donor graft antigens, leading to cell-mediated (ie, type IV hypersensitivity) rejection that typically occurs within 6 months after transplant. This type of rejection is generally reversible with increased doses of immunosuppression.

(Choice C) Degranulation of mast cells and basophils occurs during a type I hypersensitivity reaction (eg, allergic response), which is not involved in organ transplant rejection.

(Choice D) Graft versus host disease occurs when donor T lymphocytes recognize recipient antigens, leading to vasculitis and tissue damage that frequently affects the skin, liver, and gastrointestinal tract. The risk is highest with allogeneic hematopoietic stem cell transplantation.

(Choice E) Atherosclerotic stenosis of the transplanted renal artery can occur over time, but it would not cause acute graft ischemia with cyanosis and mottling at the time of transplant surgery.

Educational objective:
Hyperacute rejection is caused by preformed antibodies in the recipient that recognize and attack donor antigens (ie, type II hypersensitivity). These are often anti-ABO blood group or anti-HLA antibodies. Vascular injury and capillary thrombotic occlusion lead to rapid ischemic necrosis of the renal graft, often evidenced by gross cyanosis and mottling immediately following graft perfusion.