Features of acute rejection that increase risk for chronic rejection

Background, Acute rejection (AR) has been shown to be a significant risk fa ctor for chronic rejection (CR) in kidney transplant recipients, yet many r ecipients with AR do not progress to CR, The purpose of this study was to d etermine if certain AR episodes are associated with a worse prognosis. Methods. The study group consisted of 279 kidney transplant recipients, all treated for a single episode of biopsy-proven AR. All AR episodes were ini tially treated with steroids; steroid-resistant rejection was managed with an antibody preparation. Results. First, by univariate techniques, we determined the clinical impact of severity of AR (as estimated by delta creatinine [dCr], defined as the change in baseline serum creatinine level 6 weeks after AR treatment) on tw o different endpoints- biopsy-proven CR and graft survival. Irrespective of B-week dCr, all recipients with AR had a significantly increased risk of C R vs. those with no AR (P<0.01), Recipients with dCr between 0.5 and 1.0 mg /dl had a significantly higher incidence of CR vs. those with dCr <0.5 mg/d l (P<0.05), but a significantly lower incidence vs. those with dCr >1.0 mg/ dl (P<0.05), We then performed multivariate analysis, We used severity of A R in addition to other variables (e.g., timing of AR, donor age) to determi ne which factors were most associated with risk for CR and graft loss. Risk for CR increased with AR episodes occurring >6 months after transplant (re lative risk [RR]=3.8, P=0.005); with moderate or severe (vs, mild) AR episo des (RR=2.7, P=0.05); and with dCr >0.5 mg/dl (vs, <0.5 mg/dI) at 6 weeks a fter AR treatment (RR=2.3, P=0.1). Findings were similar when graft surviva l (death-censored) was the endpoint instead of CR, Conclusions. All AR episodes are associated with some increase in the risk for CR. But AR episodes occurring >6 months after transplant and those of i ncreased severity (as assessed qualitatively by histologic grading and quan titatively by dCr) confer the greatest risk. Recipients with these risk fac tors could be targeted with measures to decrease their risk for CR, includi ng trials of novel immunosuppressive regimens.