0041-1337/01/7206-1050/0 TRANSPLANTATION Vol. 72, 1050–1055, No. 6, September 27, 2001 Copyright © 2001 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. INDUCTION VERSUS NONINDUCTION IN RENAL TRANSPLANT RECIPIENTS WITH TACROLIMUS-BASED IMMUNOSUPPRESSION 1 GEORGES MOURAD, 2,19 VALE´ RIE GARRIGUE, 2 JEAN-PAUL SQUIFFLET, 3 TATIANA BESSE, 3 FRANC¸ OIS BERTHOUX, 4 ERIC ALAMARTINE, 4 DOMINIQUE DURAND, 5 LIONEL ROSTAING, 5 PHILIPPE LANG, 6 CHRISTOPHE BARON, 6 DENIS GLOTZ, 7 CORINNE ANTOINE, 7 PAUL VIALTEL, 8 THIERRY ROMANET, 8 YVON LEBRANCHU, 9 AZMI AL NAJJAR, 9 CHRISTIAN HIESSE 10 LUC POTAUX, 11 PIERRE MERVILLE, 11 JEAN-LOUIS TOURAINE, 12 NICOLE LEFRANCOIS, 12 MICHE` LE KESSLER, 13 EDITH RENOULT, 13 CLAIRE POUTEIL-NOBLE, 14 REMI CAHEN, 14 CHRISTOPHE LEGENDRE, 15 JEANINE BEDROSSIAN, 15 PATRICK LE POGAMP, 16 JOSEPH RIVALAN, 16 MICHEL OLMER, 17 RAJ PURGUS, 17 FRANC¸ OISE MIGNON, 18 BE´ ATRICE VIRON, 18 AND BERNARD CHARPENTIER 10 France Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. 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 ei- ther induction therapy with ATG (n151) followed by initiation of tacrolimus on day 9 or immediate tacroli- mus-based triple therapy (n158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses 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 rejec- tions were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statisti- cally significant differences in the incidence of ad- verse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 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 thrombocytopenia (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 mellitus 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 of acute rejection, but it significantly increases adverse events, particularly CMV infection. Since the late 1960s, antithymocyte (ATG) and antilym- phocyte globulins are available for antibody induction ther- apy and treatment of otherwise intractable acute rejections (1). Induction therapy in renal transplant recipients is thought to reduce the incidence of acute rejection and to prolong long-term graft survival (2, 3). Furthermore, the use of antibody induction avoids the administration of vasocon- strictive and potentially nephrotoxic immunosuppressants in the immediate posttransplantation period while it effectively prevents rejection by inhibiting T cell functions (4, 5). These beneficial effects encouraged the development of sequential treatment protocols for which ATG was given immediately after transplantation and the primary immunosuppressant was introduced when renal function was well established (6, 7). Several randomized controlled trials that analyzed kidney allograft survival after treatment with or without antibody induction therapy and cyclosporine-based regimens have failed to reveal statistically significant differences for patient survival and graft survival. However, when incidences of rejection were compared, the rates observed in treatment groups who had received induction treatment were fre- quently lower than in the noninduction groups (8 –12). Tacrolimus has emerged as an important agent for the prevention of renal allograft rejection. In a large European trial in which no induction was used, tacrolimus-based triple therapy provided a statistically significant reduction in the incidence of acute rejection compared with cyclosporine- based triple therapy (13). Similar results were obtained in a 1 This study was funded by Fujisawa GmbH. 2 Hopital Lapeyronie, Montpellier. 3 Clinique Universitaire, Bruxelles. 4 Hopital Nord, St. Etienne. 5 Hopital Rangueil, Toulouse. 6 Hopital Henri Mondor, Creteil. 7 Hopital Broussais, Paris. 8 Hopital Michallon - CHU Nord, Grenoble. 9 Hopital Bretonneau, Tours. 10 Hopital Bicetre, Le Kremlin Bicetre. 11 Hopital Pellegrin-Tripode, Bordeaux. 12 Hopital Edouard Herriot, Lyon. 13 Hopitaux de Brabois, Nancy. 14 C.H.U. Lyon-Sud, Pierre-Benite. 15 Hopital Saint-Louis, Paris. 16 C.H.R.U. Pontchaillou, Rennes. 17 Hopital de la Conception, Marseille. 18 Hopital Bichat, Paris. 19 Address correspondence to: Prof. Georges Mourad, Service de Nephrologie et Transplantation, Hopital Lapeyronie, 371 Av. Du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. 1050