12
In randomized controlled trials, elective
Cyclosporine A (CsA) withdrawal (WDL) has not affected short-term graft
survival. We retrospectively compared late, conditional graft survival
(CGS), i.e., conditional on survival at 1 year, in 751 consecutive
patients transplanted between 1/1/85 and 12/31/96 who had: 1) conventional
immunosuppression without CsA (n=177, 24%), 2) elective CsA WDL after 1
year (n=394, 52%), 3) elective continuation of CsA at the request of the
patient or private nephrologist (n=107. 14%). 41 CsA WDL due to failure or
toxicitv of CsA (n=29. 4%) or
5)
CsA continuation because of rejection or intolerance to azathioprine
(n=44, 6%). All patients received prednisone and, if possible,
azathioprine. The 3- and 6-year (Kaplan Meier) CGS were very low in groups
4 (68% and 37%) and 5 (59% and 37%), illustrating the potential fallacy of
using registry data that includes patients with non-elective CsA WDL or
non-elective CsA continuation to judge the effects of elective CsA WDL on
CGS. The 3- and 6-year CGS in groups 1, 2 and 3, respectively, were: 87%
and 76% (n=145 and 100), 94% and 76% (n=313 and 161), and 95% and 87%
(n=67 and 26), p=0.16 by Log Rank. After adjusting for differences in
multiple risk factors in a Cox proportional hazards model, there was a
trend for reduced CGS with conventional immunosuppression without CsA
(p=0.062), and a trend for reduced CGS with elective CsA WDL (p=0.065).
The cumulative incidence of acute rejection between 1 and 6 years
post-transplant was 28%, 28%, and 13% in groups 1, 2 and 3, respectively
(p=0.014). Nevertheless. according to the 1997 UNOS Center Specific Report
for kidney transplants from 1/1/88 through 4/30/92, 3-year CGS was 88.1%
at our center, which was comparable to the expected (adjusted) 87.6%
3-year CGS. We conclude that the use of CsA vs. conventional
immunosuppression, and elective CsA WDL, have had either no effect or a
small effect (p>0.05) on late graft failure at our center. The rate of
late acute rejection is the same after CsA WDL as it was before the
introduction of CsA, challenging the notion that WDL actually causes acute
rejection. A trend (p>0.05) toward improved CGS among patients who
elected to continue CsA may be due to chance, may be the result of
selection bias, or may be due to improved CGS from continued CsA
(suggesting the need for additional long-term follow-up). We speculate
that newer adjunctive immunosuppression may reduce the incidence of acute
rejection after CsA WDL and enhance long-term CGS in the future.