Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression

Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacroli mus therapy with immediate tacrolimus therapy in renal transplant recipient s. Methods. This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrol imus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid bolus es were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. Results. At month 12, biopsy-confirmed acute rejections were reported for 1 5.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incide nce of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (n oninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine pati ents died. Patient survival and graft survival at month 12 was similar in b oth treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). S tatistically significant differences in the incidence of adverse events wer e found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduct ion, 19.0%,, P=0.009), leukopenia (37.3% vs. 9.5%, P <0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thromboc ytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mell itus was 3.4% (induction) and 4.5% (noninduction). Conclusion. Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence o f acute rejection, but it significantly increases adverse events, particula rly CMV infection.