Both acute rejection and the function of a renal allograft early after transplantation correlate with long-term graft survival. In this study we assessed the relationship between these two factors in 843 adult recipients of first cadaveric renal grafts, transplanted at a single institution and followed for a minimum of 3.5 years. Patients were divided into four groups according to (1) history of acute rejection (AR) during the first 6 months after transplantation, and (2) concentration of serum creatinine at 6 months after transplantation (SCr6mo < or greater than or equal to 2 mg/dl). Death censored allograft survival was not significantly different among patients without AR and with low SCr6mo (group 1, n=376), patients without AR but with an elevated SCr6mo (group 2, n=117), and patients with AR but low SCr6mo (group 3, n=185). In contrast, graft survival was significantly worse in patients with AR and an elevated SCr6mo (group 4, n=165) compared with patients in the other three groups (Cox, P<0.0001). The elevated SCr6mo in group 4 patients was not necessarily the consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after transplantation (SCr10d), before they had AR, that was equal to or higher than the SCr6mo. Based on this observation we investigated the implications of the SCr10d concentration for graft prognosis. The SCr10d correlated weakly with graft survival (Cox, P=0.05). However, an elevated SCr10d correlated with other potential risk factors for graft survival including: Older donors (P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate regression); and posttransplant factors such as, increasing numbers of AR (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft dysfunction predicts poor graft survival only when associated with AR. Similarly, AR predicts a poor renal allograft survival only when associated with graft dysfunction. The SCr10d is an indicator of risk factors from both the donor and recipient, and an elevated SCr10d predicts a higher risk of acquiring additional risk factors early after transplantation.
