title: Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome.
abstract: BACKGROUND
  Acute rejection (AR) of the transplanted kidney has been identified as the major risk factor for the development of chronic rejection and immunological graft loss. However, the clinical presentation and response to AR therapy can vary considerably between recipients.
  
  
  METHODS
  We studied the first AR episode in 201 kidney-only recipients transplanted between January 1987 and June 1998 who were biopsied between April 1993 and June 1998 and were graded using the Banff schema. All patients received cyclosporine-based immunosuppression. There were 134 cadaver donor (66.7%) and 67 live donor (33.3%) recipients followed for a mean of 46.2 (range 4-128) months. All Banff grade 1-3 and 40/78 borderline (BL) cases were treated for rejection after biopsy. These patients were compared with a contemporaneous control population who did not experience AR. Demographic risk factors associated with graft loss were identified in both univariate and multivariate analysis. Daily (0-18) serum creatinine (SCr) values during and after the AR were plotted for each patient to generate curves and calculate area under the serum creatinine versus time curve (mg/dl/day). Four response patterns to treatment were identified according to the velocity of % increase (V1) and decrease (V2) of serum creatinine. These were identified as rapid rise and fall (n=62); rapid rise and slow fall (n=43); slow rise and fall (n=55); and slow rise and rapid fall (n=41). Kaplan-Meier graft survivals were compared between the groups.
  
  
  RESULTS
  Any Banff grade was associated with increased risk for graft loss (P=0.0001). However, no significant differences were observed between the Banff BL and B1-3 groups, or among those BL patients who were treated or remained untreated for AR. Multivariate analysis identified a black recipient (P=0.03, risk ratio 2.0) and area under the serum creatinine versus time curve (P=0.0001, risk ratio 3.2) as significant risk factors for graft loss. The AR response pattern RS resulted in a significantly (P=0.0072) diminished 5-year graft survival (45%) compared with the other groups. Serum creatinine pattern, but not Banff grade, was also a significant (P=0.025) predictor of re-rejection.
  
  
  CONCLUSIONS
  These data suggest that all Banff grades, including BL, carry a significant risk for graft loss, and the initial response to antirejection therapy can predict long-term graft outcome. They support the practice of treating AR promptly and definitively and suggest that the RS subgroup of rejecting grafts could be targeted for additional antirejection therapy. This subgroup can be identified by 10 days of AR therapy, and should be the subject of further study.
authors.affiliation: Department of Urology, Section of Renal Transplantation, The Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ishikawa
authors.forename: S M
authors.initials: SM
authors.lastname: Flechner
authors.forename: D A
authors.initials: DA
authors.lastname: Goldfarb
authors.forename: J L
authors.initials: JL
authors.lastname: Myles
authors.forename: C S
authors.initials: CS
authors.lastname: Modlin
authors.forename: N
authors.initials: N
authors.lastname: Boparai
authors.forename: D
authors.initials: D
authors.lastname: Papajcik
authors.forename: B
authors.initials: B
authors.lastname: Mastroianni
authors.forename: A C
authors.initials: AC
authors.lastname: Novick
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D003401:Creatine / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D003401:Creatine