title: The impact of late acute rejection after cadaveric kidney transplantation.
abstract: BACKGROUND
  Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period.
  
  
  OBJECTIVE
  To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR).
  
  
  METHODS
  687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival.
  
  
  METHODS
  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 baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared.
  
  
  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 failure 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% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR 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 frequency 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 and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non-compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.
authors.affiliation: Department of Transplantation Surgery, University of Glasgow and the Western Infirmary, Glasgow, UK.
authors.forename: J T
authors.initials: JT
authors.lastname: Joseph
authors.forename: D B
authors.initials: DB
authors.lastname: Kingsmore
authors.forename: B J
authors.initials: BJ
authors.lastname: Junor
authors.forename: J D
authors.initials: JD
authors.lastname: Briggs
authors.forename: Y
authors.initials: Y
authors.lastname: Mun Woo
authors.forename: B C
authors.initials: BC
authors.lastname: Jaques
authors.forename: D N
authors.initials: DN
authors.lastname: Hamilton
authors.forename: A G
authors.initials: AG
authors.lastname: Jardine
authors.forename: R M
authors.initials: RM
authors.lastname: Jindal
mesh_terms: D000208:Acute Disease; D000328:Adult; D002102:Cadaver; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D006084:Graft Rejection / Q000145:classification* / Q000453:epidemiology; D006085:Graft Survival; D006680:HLA Antigens; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine