title: Determinants of chronic renal allograft rejection in cyclosporine-treated recipients.
abstract: 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 > or = 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 > or = 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 long-term 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.
authors.affiliation: Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Flechner
authors.forename: C S
authors.initials: CS
authors.lastname: Modlin
authors.forename: D P
authors.initials: DP
authors.lastname: Serrano
authors.forename: D A
authors.initials: DA
authors.lastname: Goldfarb
authors.forename: D
authors.initials: D
authors.lastname: Papajcik
authors.forename: B
authors.initials: B
authors.lastname: Mastroianni
authors.forename: M
authors.initials: M
authors.lastname: Goormastic
authors.forename: A C
authors.initials: AC
authors.lastname: Novick
mesh_terms: D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine