Both acute rejection and the function of a renal allograft early after
transplantation correlate with long-term graft survival. In this stud
y we assessed the relationship between these two factors in 843 adult
recipients of first cadaveric renal grafts, transplanted at a single i
nstitution and followed for a minimum of 3.5 years. Patients were divi
ded 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 gr
eater than or equal to 2 mg/dl). Death censored allograft survival was
not significantly different among patients without AR and with low SC
r6mo (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 wit
h 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 patien
ts in group 4 had a SCr at 10 days after transplantation (SCr10d), bef
ore they had AR, that was equal to or higher than the SCr6mo. Based on
this observation we investigated the implications of the SCr10d conce
ntration for graft prognosis. The SCr10d correlated weakly with graft
survival (Cox, P=0.05). However, an elevated SCr10d correlated with ot
her potential risk factors for graft survival including: Older donors
(P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.00
01, all by multivariate regression); and posttransplant factors such a
s, increasing numbers of AR (P<0.0001), higher posttransplant blood pr
essure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by m
ultivariate regression). In conclusion, graft dysfunction predicts poo
r graft survival only when associated with AR. Similarly, AR predicts
a poor renal allograft survival only when associated with graft dysfun
ction. The SCr10d is an indicator of risk factors from both the donor
and recipient, and an elevated SCr10d predicts a higher risk of acquir
ing additional risk factors early after transplantation.