Immunologic factors: The major risk for decreased long-term renal allograft survival

Background. Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss, Differentiating between these two factors is important because preven tion strategies differ. Methods. To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underw ent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft, loss as a result of death w ith function, technical failure, primary nonfunction, and recurrent disease , leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who wo uld be at risk for graft loss secondary to both immunologic and nonimmunolo gic factors. These recipients were analyzed in the following 2 groups: thos e treated for a previous episode of acute rejection (AR) (Group 1; n=588; 3 28 CAD, 260 LD) and those with no AR (Group 2: n=999; 429 CAD, 570 LD). Act uarial graft survival and causes of graft loss were determined for each gro up, Presumably, graft loss in Group 1 would be caused by immunologic and no nimmunologic factors; graft loss in Group 2 would be caused primarily by no nimmunologic factors. Results. The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P <0.001 vs. Group 2), Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; disconti nuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P=0.001 vs. Group 2). Conclusions. This very low incidence of chronic rejection in recipients wit hout previous AR suggests that immunologic factors are the main determinant s of long-term kidney transplant outcome; nonimmunologic factors in isolati on may have only a minimal impact on long-term graft survival.