A RANDOMIZED TRIAL COMPARING CYCLOSPORINE INDUCTION WITH SEQUENTIAL THERAPY IN RENAL-TRANSPLANT RECIPIENTS

Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA ), allowing CsA to be introduced immediately after renal transplantati on and thereby obviating the need for sequential induction therapy wit h a monoclonal or polyclonal antibody, To test this hypothesis, in a p ilot feasibility trial 100 cadaveric or one-haplotype-mismatched livin g-related renal transplant recipients were randomized to either (1) se quential therapy with antithymocyte globulin (ATG) (ATGAM; Upjohn, Kal amazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was estab lished and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Car dizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release tw ice 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-s quare analysis), Graft failures (10% v 16%; P = 0.372) and the inciden ce 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 10(3) v 197 +/- 75 x 10(3) at 7 days; P < 0.001) and lower white blood cell counts (9.6 +/- 4.6 x 10(3) v 12.3 +/- 4.9 x 10(3) at 7 day s; 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 levels at days 1, 3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that proph ylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation. (C) 1997 by the National Kidney Foundation, Inc.