In our experience the use of
OKT3 as prophylaxis in
renal transplantation has been associated with an increased incidence of both
delayed graft function and
thromboses of graft vessels.
OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent
pulmonary edema and by the use of very high dose (30 mg/kg) of
methylprednisolone (mPDS) before the first
OKT3 injection to reduce the release of
cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the
calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of
transplantation; and (3) the dose of mPDS given before the first
OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of
delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of
pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft
thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/
diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of
delayed graft function and graft vessels
thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of
steroids before the first
OKT3 injection, administration of a
calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against
OKT3 nephrotoxic effects.