PREVENTION OF OKT3 NEPHROTOXICITY AFTER KIDNEY-TRANSPLANTATION

In our experience, the use of OKT3 as prophylaxis in renal transplanta tion has been associated with an increased incidence of both delayed g raft function and thromboses of graft vessels. OKT3 nephrotoxicity mig ht have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of Very high dose (30 mg/kg) o f methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative mana gement in three ways: (1) hydration status was optimalized; (2) the ca lcium-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, c ontrol patients, N = 172; group 2. managed as described above, N = 173 ) showed that: (1) the incidence of delayed graft function fell from 5 2% in group 1 to 22% in group 2 (P < 0.0001); (2) the incidence of pul monary 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). Multivariat e analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the red uced occurrence of delayed graft function and graft vessels thrombosis , respectively. We conclude that a combined strategy of appropriate do sage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and effi ciently prevents against OKT3 nephrotoxic effects.