Early versus late acute rejection episodes in renal transplantation

Acute rejection is a major complication after renal transplantation and the most important risk factor for chronic rejection. We investigated whether the timing of the last treated acute rejection episode (ARE) influences long-term outcome and compared the risk profiles of early versus late ARE.

A cohort of 654 patients who underwent cadaveric renal transplants (1983-1997) that functioned for more than 6 months was studied. In 384 of 654 transplant recipients, one or more treated AREs were documented; the last ARE occurred in 297 of 384 transplant recipients within 3 months and in 87 of 384 after 3 months. Applying multivariate logistic regression analysis, we compared the predictor variables of the two groups with transplants without AREs.

Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%, 86%, and 45% for patients without ARE, with early ARE, and with late ARE, respectively. Delayed graft function, odds ratio (OR) 2.37 (1.55-3.62), and major histocompatibility complex (MHC) class II incompatibility, OR 2.28 (1.62-3.20) per human leukocyte antigen (HLA)-DR mismatch, were independent risk factors for early ARE. In contrast, recipient age, OR 0.75 (0.61-0.93) per 10-year increase, donor age, OR 1.28 (1.07-1.53) per 10-year increase, female donor gender, OR 1.74 (1.03-2.94), and MHC class I incompatibility, OR 1.35 (1.07-1.72) per mismatch of cross reactive groups, were associated with late ARE.

Late ARE has a detrimental impact on long-term graft survival and is associated with MHC class I incompatibility, whereas early ARE is correlated with HLA-DR mismatches and has a better prognosis. These data are consistent with the role of direct and indirect allorecognition in the pathophysiology of early and late ARE, respectively.