Flechner S M, Modlin C S, Serrano D P, Goldfarb D A, Papajcik D, Mastroianni B, Goormastic M, Novick A C
Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA.
Transplantation. 1996 Nov 15;62(9):1235-41. doi: 10.1097/00007890-199611150-00009.
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.
我们分析了1987年7月至1994年11月期间507例患者中511例单纯肾移植慢性排斥反应的发生情况。为年龄≥18岁、接受以环孢素为基础的免疫抑制治疗且移植肾存活至少12个月的受者建立了一个数据库。347例尸体供肾移植受者（67.9%）和164例活体供肾移植受者（32.1%）接受了12至102个月的随访（平均51个月）。124例移植肾（24%）被诊断为慢性排斥反应，诊断的平均时间为23±18个月（范围3至92个月）。使用Cox模型进行多因素分析以确定危险因素。在单因素模型中分析排斥反应发作的时间和严重程度的影响。慢性排斥反应的存在导致尸体供肾移植受者（83.7%对58.2%）和活体供肾移植受者（93.2%对53.1%）的5年移植肾存活率均下降（P=0.0001）。慢性排斥反应发生的显著变量包括急性排斥反应发作（P=0.0001）、黑人受者（P=0.0006）、供者年龄≥50岁（P=0.006）以及移植后6个月时血清肌酐水平>2.0mg/dl。以血清肌酐峰值或治疗后恢复至基线水平衡量的排斥反应严重程度与慢性排斥反应无关。然而，持续超过5天（P=0.03）或在6个月后发生（P=0.001）的急性排斥反应发作确实会影响慢性排斥反应的发生时间。此外，供受者种族不匹配是尸体供肾移植受者的一个显著危险因素（P=0.008）。我们得出结论，急性排斥反应是慢性排斥反应最显著的危险因素，移植肾的长期转归可能早在最初6个月就已确定。供受者种族匹配可能有助于将慢性排斥反应风险降至最低。减少急性排斥反应发生率和严重程度的未来进展可能对长期存活产生最大影响。
