A RANDOMIZED DOUBLE-BLIND TRIAL OF THE USE OF HUMAN RECOMBINANT SUPEROXIDE-DISMUTASE IN RENAL-TRANSPLANTATION

Oxygen free radical generation has been implicated as a possible mediator of the reperfusion injury postulated to occur following revascularization of the cold preserved and transplanted kidney. The superoxide radical (O2-) scavenger, superoxide dismutase, from bovine or recombinant (rh-SOD) sources, may ameliorate oxygen-free-radical mediated reperfusion injury of transplanted kidneys. To test this hypothesis, we performed a prospective, randomized, double-blind trial of the use of human rh-SOD in renal transplantation at three participating centers. Half of a 20 mg/kg solution of rh-SOD or placebo was administered as a bolus intravenous injection immediately prior to renal allograft reperfusion and the remainder as a peripheral intravenous infusion for 1 hr thereafter. Posttransplant renal function was determined using Tc-99-DTPA clearance to measure glomerular filtration rate at 48 +/- 24 hr and day 6 posttransplant. A two-tailed t test was used for pooled data, and analysis of variance was used to evaluate between center differences in outcome. One hundred and sixteen patients (58 rh-SOD and 58 placebo) were entered into the study. No adverse reactions to rh-SOD or placebo were noted. No differences were noted between rh-SOD and placebo groups with regard to GFR at 48 hr, serum creatinine or creatinine clearance at day 6, or percentage of patients with GFR less-than-or-equal-to 10 ml/min or less-than-or-equal-to 5 ml/min at 48 hr. The data did not vary when analyzed by center or in aggregate form, and no correlation was noted between storage time and GFR in either group. We conclude that data from this trial provide little basis for the use of rh-SOD as described to ameliorate reperfusion injury in transplanted kidneys.