THE BENEFICIAL EFFECT OF HUMAN RECOMBINANT SUPEROXIDE-DISMUTASE ON ACUTE AND CHRONIC REJECTION EVENTS IN RECIPIENTS OF CADAVERIC RENAL-TRANSPLANTS

In a prospective randomized double-blind placebo controlled trial, the effect of rh-SOD, given in a dose of 200 mg intravenously during surg ery to cyclosporine-treated recipients of cadaveric renal allografts, on both acute and chronic rejection events as well as patient and graf t survival was investigated by analyzing the patients' charts retrospe ctively. The results obtained show that rh-SOD exerts a beneficial eff ect on acute rejection events as indicated by a significant reduction of (1) first acute rejection episodes from 33.3% in controls to 18.5%, as well as (2) early irreversible acute rejection from 12.5% in contr ols to 3.7%. With regard to long-term results, there was a significant improvement of the actual 4-year graft survival rate in rh-SOD-treate d patients to 74% (with a projected half-life of 15 years) compared wi th 52% in controls (with an extrapolated half-life of 5 years). The be neficial effect of rh-SOD observed in this trial is not fully understo od, although one can assume that the effect is related to its antioxid ant action on ischemia/reperfusion injury of the renal allograft, ther eby potentially reducing the immunogenicity of the graft. In addition and in accordance with the ''response-to-injury hypothesis'' in the pa thogenesis of general atherosclerosis, rh-SOD has the potential to mit igate free radical-mediated reperfusion injury-induced acute endotheli al cell damage that potentially may contribute to the process of chron ic obliterative rejection arteriosclerosis.