Transitioning of renal transplant pathology from allograft to xenograft and tissue engineering pathology: Are we prepared?

Table 1 Classification and diagnostic criteria used in pig-to-primate solid organ transplantation pathology

Hyperacute rejection	Acute humoral xenograft rejection	Acute cellular xenograft rejection
Time period
Immediately after reperfusion of the graft (typically within 24 h)	Later after reperfusion (after 24 h)	After 3 d
Immediate graft function
No (no urine since reperfusion)	Yes, urine formation initially	Yes, urine formation initially
Histopathologic features
Massive hemorrhage; Immunoglobulin and fibrin deposition; Complement (C5b-9) deposition; Presence of neutrophils; Thrombosis, ±	Hemorrhage present; Immunoglobulin and fibrin deposition; Complement (C5b-9) deposition; Presence of neutrophils; Lymphocytes may be present; Necrosis and transmural infiltration by neutrophils in blood vessels can be present; Apoptosis may be present; Thrombosis present	No hemorrhage; Immunoglobulin and fibrin deposition, rare; Complement, ±; Presence of mononuclear (lymphoid) cells associated with tissue destruction (e.g., tubulitis); No thrombosis

Table 2 Types of chronic xenograft vasculopathy

Type of vasculopathy	Histopathological features
Chronic humoral rejection-associated vasculopathy	Arterial intimal thickening; Presence of TUNEL+ cells; Deposits of fibrin, immunoglobulins (IgG and IgM), and complement components (C3, C4d, and C5b-9)
Chronic cellular rejection-associated vasculopathy	Mononuclear cell infiltration in the neointima; Active endothelialitis; TUNEL+ cells
Combined chronic humoral and cellular rejection-associated vasculopathy	Fibrinoid material deposition and cellular infiltration in the arterial neointima with immunoglobulin and complement deposition and infiltration of T cells, macrophages, and polymorphonuclear leukocytes
Fully developed vasculopathy	Narrowing of arteries with a fibrotic neointima, but without fibrinoid material, or cellular infiltration

TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling.