CHRONIC RENAL-ALLOGRAFT REJECTION - IMMUNOLOGICAL AND NONIMMUNOLOGICAL RISK-FACTORS

The pathogenesis of chronic renal allograft rejection is unknown. It i s also unclear why cyclosporine has failed to prevent chronic rejectio n. We examined possible risk factors for graft loss to chronic rejecti on among 706 renal transplants using the Cox proportional hazards mode l with fixed and time-dependent covariates. Both the number and the se verity of acute rejection episodes were independent risk factors for c hronic rejection [relative risk (95% confidence interval) 2.31 (2.04 t o 2.60) and 1.53 (1.27 to 1.84), respectively]. Cyclosporine and cyclo sporine withdrawal had no effect on chronic rejection. Acute rejection s occurring within the first three months after transplantation, when cyclosporine most effectively prevented acute rejection, also had no e ffect on chronic rejection. Risk factors that were independent of acut e rejection and not clearly attributable to immune mechanisms included serum albumin [0.20 (0.10 to 0.38) for each g/dl], proteinuria [1.42 (1.29 to 1.57) for each g/24 hr], and serum triglycerides [1.09 (1.03 to 1.16) for each 100 mg/dl]. These results suggest that the reduction in acute rejection episodes from cyclosporine has failed to reduce gr aft failure from chronic rejection, possibly because the early (within the first 3 months) and mild acute rejection episodes that are most e ffectively prevented by cyclosporine do not cause chronic rejection. I n addition, the results suggest that there may be a number of nonimmun ologic risk factors for chronic rejection.