The impact of late acute rejection after cadaveric kidney transplantation

Background: Acute graft rejection (AR) following renal transplantation resu lts in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term g-raft and, patient outcome of AR occur ring late in the post-transplant period. Aim: To determine if rejection episodes can be classified by time from tran splantation by their impact on graft survival into early acute rejection (E AR) and late acute rejection (LAR). Materials and methods: 687 consecutive adult renal transplant recipients wh o received their first cadaveric renal transplant at a single centre. All r eceived cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical record s, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. Analysis: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a base line, we determined the relative risk of graft failure by time to rejection . The characteristics of patients who had no rejection, EAR and LAR were co mpared. Results: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft fail ure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p < 0.001). Seventy-eight patients (11 .4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p < 0.003). The 5-yr graft survival for those who had LAR was 45% an d 10-yr survival was 28%. HLA mismatches were more frequent in those with E AR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA -DR: 63 vs. 41%, p < 0.003). There was no difference in mismatching frequen cy between NAR and LAR. Conclusions: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early a nd late phases. In view of the very poor graft survival associated with LAR , it is important to gain further insight into the main aetiological factor s. Those such as suboptimal CyA blood levels and non-compliance with medica tion should be further investigated with the aim of developing more effecti ve immunosuppressive regimens in order to reduce the incidence of LAR.