THE IMPACT OF ACUTE REJECTION EPISODES ON LONG-TERM GRAFT FUNCTION AND OUTCOME IN 1347 PRIMARY RENAL-TRANSPLANTS TREATED BY 3 CYCLOSPORINE REGIMENS

To characterize factors of importance for the occurrence of acute reje ction as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were s tudied in 951 primary cadaveric donor kidney recipients (CD) and in 39 6 primary living donor kidney recipients (LD). The patients were treat ed by three immunosuppressive schedules, namely, CsA given in a high d ose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence o f acute rejection was higher and occurred earlier after transplantatio n in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence o f first acute rejection was similar in CD and LD patients, 59.1% vs. 6 0.6%, it was successfully reversed by antirejection treatment in a hig her percentage in LD patients. The estimated graft half-life was short er in patients who had acute rejection episodes than those who did not , 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poor er in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 4 5-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejec tion were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-ma tch, young recipient age, disease of diabetes mellitus, and HLA-DR mis matching. In LD recipients, the corresponding risk factors were treatm ent schedule, young recipient, HLA mismatching, and transplantation fr om parent to child. Thus, the study has demonstrated some factors of i mportance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graf t survival and renal function. These results suggest that a primary ai m of future treatment strategies should be to reduce the incidence of these episodes.