Chronic rejection in renal transplantation

Chronic rejection in renal transplantation is an alloantigen-dependent immune process ultimately leading to graft failure. We reviewed the literature on the basis of the case history of a patient who lost her renal allograft apparently from chronic interstitial rejection. Chronic rejection presents clinically as chronic transplant dysfunction starting at various intervals after transplantation. The histopathologic features consist of chronic allograft nephropathy with or without transplant vasculopathy or glomerulopathy. Chronic rejection should be differentiated from chronic toxicity of calcineurin inhibitors, de novo or recurrent glomerulonephritis, polyoma (BK) virus nephropathy, transplant renal artery stenosis, and nephrosclerosis. Young recipient age, black race, presensitization, histoincompatibility, and acute, especially vascular, and late acute rejection episodes are dominant risk factors, compatible with immunologic mechanisms. Cellular and humoral responses resulting from indirect recognition of alloantigens with subsequent fibrotic sequelae play a central role in the pathogenesis. Circulating donor-specific antibodies and staining for C4d can detect humoral chronic rejection. The prognosis depends on alloreactivity and the presence of progression factors such as old donor age, renal dysfunction, proteinuria, hyperlipidemia, and smoking. A multifactorial approach directed to the risk and progression factors is needed to prevent premature graft loss from chronic rejection.