A PROSPECTIVE RANDOMIZED COMPARISON OF QUADRUPLE VERSUS TRIPLE THERAPY FOR 1ST CADAVER TRANSPLANTS WITH IMMEDIATE FUNCTION

In January 1988, we initiated a prospective, randomized comparison of prophylactic antilymphoblast globulin (ALG; quadruple therapy) versus no prophylactic ALG (triple therapy) in the setting of immediate graft function (defined by a brisk diuresis and a 20% decline in serum crea tinine within 24 hr). Recipients were stratified according to presence of diabetes and age greater or less than 50 years. Recipients on quad ruple therapy (n=61) received 7 days of prophylactic Minnesota ALG (5 mg/kg on day 1, 10 mg/kg on day 2, 20 mg/kg on days 3-7). CsA, 10 mg/k g/day, began on day 6. AZA began at 2.5 mg/kg/day and was adjusted acc ording to white blood cell count. Recipients on triple therapy (n=60) began immediate CsA, 10 mg/kg/day orally and AZA, 5 mg/kg/day, taperin g to 2.5 mg/kg/day by day 8. Both groups received identical prednisone tapers beginning at 1 mg/kg/day, decreasing to 0.5 mg/kg/day by 2 wee ks and to 0.15 mg/kg/day by 6 months. Demographic characteristics betw een groups were not different with respect to diabetes, age, sex, race , per cent panel-reactive antibodies (PRA), or HLA matching. Follow-up ranged from 2 to 4.5 years. Patient survival was 93% for the quadrupl e therapy group and 90% for triple therapy. Actuarial graft survival w as 79% in the quadruple group and 72% in the triple group (P=0.18). Gr aft loss due to rejection oocurred in 6/61 receiving ALG versus 7/60 i n the immediate CsA group. Three of 4 high PRA recipients in the immed iate CsA group lost their grafts within 30 days compared with none in the ALG group. The mean time to graft loss was significantly longer fo r the quadruple therapy group (17+/-8 months) compared with the triple therapy group (4+/-5 months), P=0.006. The total number of rejection episodes was similar for both groups (29/61 vs. 31/60), as was the num ber who were rejection free (51% vs. 47%). The use of OKT3 was also si milar between groups (28% vs. 30%). The quadruple therapy group had a higher incidence of CMV infection: 20% vs. 7% (P<0.05), but no grafts or patients were lost as a result. Serum Cr was not different at 1 and 12 months (1.5 and 1.6 vs. 1.6 and 1.7, respectively), nor were Cr cl earances (63 and 68 vs. 60 and 63). Conclusion. Early initiation of or al CsA in the setting of immediate graft function is not associated wi th significant nephrotoxicity. In first cadaver transplants, prophylac tic ALG (for 7 days) does not reduce the incidence of rejection or les sen the use of OKT3. It does lengthen the time to graft loss and may p rotect high PRA recipients from early graft loss. Ultimately, patient survival, graft survival, and graft function are not significantly dif ferent as a result of these two induction protocols.