NEW TRIAL OF BASILIXIMAB-BASED IMMUNOSUPPRESSIVE REGIMEN FOR RENAL TRANSPLANTATION –JAPANESE SOUTHERN ISLAND MULTI-CENTER TRIAL -

A77 Purpose: The purpose of this study is to investigate the effect of a modified regimen of basiliximab-based immunosuppression on renal transplantation in Japan. Background: As for the use of cyclosporine A (CYA), early oral administration of Neoral and dose adjustment based on AUC0-4 or C2 instead of trough level have been recommended. Fixed dose of mycophenolate mofetil (MMF), 1.5 to 2 g per day is now widely accepted instead of azathioprine. Since the release of basiliximab in Japan two years ago, it has been reported to reduce the incidence of acute rejection and the possibility of decreasing calcineurin inhibitors and/or steroids. However, we experienced some difficult cases to control the dose or infectious episodes. Methods: The characteristics of new trial were as follows; 1) basiliximab administered 20mg at day 0 and day 4, 2) intravenous application of calcineurin inhibitors (either CYA or tacrolimus) for a few days, 3) dose adjustment with targeting average or trough level of 150-200 ng/ml for Neoral and 10-15 ng/ml for tacrolimus (TAC), 4) low dose of MMF administered 30 mg/kg daily and gradual decrease, 5) as for steroids, methyl-predonisolone 500 mg given just before reperfusion and quick decrease. In association with four transplantation centers in Kyushu and Okinawa islands, we analyzed 34 patients who underwent renal transplantation from June 2002 to March 2004. The patients were classified into CYA group (n=17) and TAC group (n=17), and compared dose-concentration relationship, graft function, rejection and infection rates, and overall efficacy. Results: The total analysis of 34 patients were as follows; average recipient age of 40.9 years old (3 to 63 y.o.), 21 male and 12 female, 22 from living donors and 12 from non-heart-beating donors, and average donor age of 55.2 y.o. (17 to 77 y.o.). The dose and concentration of CYA were 1.973 mg/kg/day and 242.3 ng/ml during DIV, 187.3 mg/day orally and 170.8 ng/ml at 4 weeks, and 150.7 mg/day and 154.6 ng/ml at discharge. Similarly, the dose and concentration of TAC were 0.042 mg/kg/day and 16.9 ng/ml during DIV, 8.5 mg/day orally and 11.4 ng/ml at 4 weeks, and 6.2 mg/day and 9.2 ng/ml at discharge. The serum creatinines in CYA and TAC groups were 3.10 vs 1.45 mg/dl at 1week, 1.99 vs 1.77 mg/dl at 4 weeks, 1.01 vs 1.28 mg/dl at minimum, and 1.17 vs 1.58 mg/dl at discharge, respectively (p=n.s.). Acute rejection within 30 days occurred 4/17 (23.5%) vs 2/17 (11.8%) cases (p=n.s.), and infection within 60 days were observed in 7/17 (41.2%) vs 5/17 (29.4%) cases (p=n.s.). Twenty nine out of 34 cases (73.5%) showed neither rejection nor infection. Thirty-one grafts (97.1%) functioned well for follow up periods (range from 1 month to 19 months). One patient in TAC group died of sepsis at day 41. Conclusions: The proposed regimen composed of basiliximab, CYA or TAC intravenous administration followed by an oral dose controlled with trough level, reduced dose of MMF and steroid decrease, would be easy to use and effective for rejection control.