Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with anti- thymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 clays until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dew, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 ± 59 x 103 v 197 ± 75 x 103 at 7 days; P < 0.001) and lower white blood cell counts (9.6 ± 4.6 x 103 v 12.3 ± 4.9 x 103 at 7 days; P = 0.003). Diltiazem reduced the dose of CsA required to maintain target blood levels (479 ± 189 mg/d v 576 ± 178 mg/d at 14 days; P = 0.015). There were no statistically significant differences between the groups in serum creatinine level at days 1,3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that prophylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation.
- Anti-thymocyte globulin
- Renal transplantation