INDIVIDUALIZATION OF IMMEDIATE POSTTRANSPLANT IMMUNOSUPPRESSION

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Abstract
In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell .gtoreq. 30% in the first 30 hr (immediate function) were started on CsA and prednisone (P) (group 1, n=26). The remainder were randomized to P and azathioprine (group 2, n=32) or P and ALG (group 3, n=26), and switched to CsA when serum Cr fell > 30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P < .05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3 (NS). In patients requiring dialysis, mean daily off dialysis was 12 .+-. 3 in both groups 2 and 3. Mean hospital stay was 12.5 .+-. 1.3 days for group 1, 21.6 .+-. 2.1 days for groups 2 (P < .05 vs. 1 and 3), and 14.5 .+-. 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P < .05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P < .05 vs. 1 and 3) and 35% of group 3 (P < .05 vs. 1 and 2). Mean serum creatinine at 6-12 months remained higher in patients with DGF (group 1 P < .05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups. There was no difference between groups in the incidence of infection. We conclude that: (1) with individualization of immunosuppression, graft survival is equivalent with and without DGF; (2) Cr remains higher in patients with DGF; (3) in patients with DGF, ALG or azathioprine in the immediate postoperative period gives equivalent graft survival; prophylactic ALG is associated with significantly decreased early rejection and hospital stay, and with more patients remaining rejection free.