Determinants of chronic renal allograft rejection in cyclosporine-treated recipients

We analyzed the development of chronic rejection in 511 kidney-only renal transplants in 507 patients between July 1987 and November 1994, A database was established for recipients greater than or equal to 18 years old who received cyclosporine-based immunosuppression and demonstrated graft survival for a minimum of 12 months. The 347 recipients of cadaver transplants (67.9%) and 164 recipients of live donor transplants (32.1%) were followed for 12 to 102 months (mean 51 months). Chronic rejection was diagnosed in 124 transplants (24%), with a mean time to diagnosis of 23+/-18 months (range 3-92), Risk factors were identified in a multivariate analysis using the Cox model, The impact of the timing and severity of rejection episodes was analyzed in a univariate model. The presence of chronic rejection resulted in decreased (P=0.0001) 5-year graft survival for both cadaver graft (83.7% vs, 58.2%) and live donor graft (93.2% vs. 53.1%) recipients, Significant variables for the development of chronic rejection included an acute rejection episode (P=0.0001), a black recipient (P=0.0006), donor age greater than or equal to 50 years (P=0.006), and a serum creatinine level >2.0 mg/dl by 6 months after transplantation. Severity of rejection measured by peak serum creatinine or posttreatment return to baseline was not related to chronic rejection. However, acute rejection episodes lasting for more that 5 days (P=0.03) or occurring after 6 months (P=0.001) did influence time to chronic rejection, In addition, mismatching for donor-recipient race was a significant (P=0.008) risk factor for recipients of cadaver grafts. We conclude that acute rejection is the most significant risk factor for chronic rejection, and the longterm fate of grafts may be determined as early as the first 6 months. Racial matching of donor-recipient pairs may be useful to minimize chronic rejection risk, Future advances that diminish the incidence and severity of acute rejection may have the greatest impact on long-term survival.