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acute rejection

Tuesday 10 March 2009

Acute Rejection. This may occur within days of transplantation in the untreated recipient or may appear suddenly months or even years later, after immunosuppression has been employed and terminated. As suggested earlier, acute graft rejection is a combined process in which both cellular and humoral tissue injuries contribute. In any one patient, one or the other mechanism may predominate. Histologically, humoral rejection is associated with vasculitis, whereas cellular rejection is marked by an interstitial mononuclear cell infiltrate.

Acute cellular rejection

An acute cellular rejection is most commonly seen within the initial months after transplantation and is heralded by an elevation of serum creatinine levels followed by clinical signs of renal failure. Histologically, there may be extensive interstitial mononuclear cell infiltration and edema as well as mild interstitial hemorrhage.

As might be expected, immunoperoxidase staining reveals both CD4+ and CD8+ lymphocytes, and these cells express markers of activated T cells, such as the α chain of the IL-2 receptor. Glomerular and peritubular capillaries contain large numbers of mononuclear cells that may also invade the tubules, causing focal tubular necrosis.

In addition to causing tubular damage, CD8+ cells may also injure vascular endothelial cells, causing a so-called endothelitis. This form of cell-mediated vascular damage is limited to the endothelium and is distinct from the antibody-mediated vasculitis described later.

The affected vessels have swollen endothelial cells, and at places the lymphocytes can be seen between the endothelium and the vessel wall. The recognition of cellular rejection is important because, in the absence of an accompanying arteritis, patients promptly respond to immunosuppressive therapy.

Cyclosporine, a widely used immunosuppressive drug, is also nephrotoxic, and hence the histologic changes resulting from cyclosporine may be superimposed.

Acute humoral rejection

Acute humoral rejection (rejection vasculitis) is mediated primarily by antidonor antibodies, and hence it is manifested mainly by damage to the blood vessels.

This may take the form of necrotizing vasculitis with endothelial cell necrosis, neutrophilic infiltration, deposition of immunoglobulins, complement, and fibrin, and thrombosis.

Such lesions are associated with extensive necrosis of the renal parenchyma. In many cases, the vasculitis is less acute and is characterized by marked thickening of the intima by proliferating fibroblasts, myocytes, and foamy macrophages.

The resultant narrowing of the arterioles may cause infarction or renal cortical atrophy. The proliferative vascular lesions mimic arteriosclerotic thickening and are believed to be caused by cytokines that cause growth of vascular smooth muscles.

See also

- allograft regection