MULTIVARIATE ANALYSIS OF RISK FACTORS IMPACTING ON IMMEDIATE AND EVENTUAL CADAVER ALLOGRAFT SURVIVAL IN CYCLOSPORINE-TREATED RECIPIENTS

Abstract

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft nonfunction adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.