A RANDOMIZED TRIAL COMPARING CYCLOSPORINE WITH ANTILYMPHOBLAST-GLOBULIN—AZATHIOPRINE FOR RENAL ALLOGRAFT RECIPIENTS

Abstract

Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG--azathioprine (AZA)--prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84% and 83%, respectively at 4 years. Corresponding graft survival is 70% and 63% for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70% for CsA-treated and 53% for ALG-AZA-treated recipients (P = .035). In the CsA group, 71% required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3 +/- 16.4 months posttransplant with mean serum creatinine of 2.40 +/- .67, current serum creatinine is 1.79 +/- .63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73 +/- .60) vs. ALG-AZA-pred (1.49 +/- .59), P = .014, even though most CsA-treated patients were eventually switched. The causes of graft loss are not different between CsA and ALG-AZA randomized patients. In nondiabetics, rejection is the most common cause of graft loss (17/33), whereas in diabetics loss due to complications from overimmunosuppression or death from cardiovascular events is significantly more common (27/44) than corresponding losses in nondiabetics (6/33, P less than .05). Switching does not seem to influence the incidence or cause of graft loss. Since most patients started on CsA-prednisone are ultimately switched to triple drug therapy, the latter is now the preferred initial treatment modality.