Donor-specific IgG antibody and the chronic rejection of human renal allografts.

Although many investigators have felt that humoral antibody was responsible for chronic rejection, attempts to detect it in the sera of recipients in the presence of functioning renal allografts have been largely unsuccessful. A modification of the mixed antiglobulin reaction has increased its sensitivity so that the development of low titers of immunoglobulin (IgG) antibody antibody specific for donor kidney cells can be detected in renal allograft recipients while renal function is still good. Donor-specific antibody was detected in the sera of 11 of 13 patients whose transplants had ceased to function from 5 to 43 months after transplantation. In five recipients the antibody was present prior to as well as after transplantation and in six recipients antibody developed after transplantation from 3 to 25 months prior to the cessation of function. In the patients with antibody, chronic rejection was characterized by hypertension which required treatment with multiple drugs, by proteinuria of greater than one gram per day, by a gradual, progressively rising serum creatinine, and by an absence of acute ologuric rejection episodes. Pathologically there was extensive intimal proliferation and occlusion of the intrarenal arteris. There also was significant glomerulonephritis which consisted of thickening of the basement membranes, mesangial cell proliferation, simplification of the capillary loops, and in some patients fibroepithelial crescent formation. These findings suggest that IgG antibodies directed against cell-surface antigens of the donor are the chief cause of chronic renal allograft rejection.