(Aims) Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day. The widespread use of a 4-drug therapy (calcineurin inhibitor (CNI), Basiliximab (Bas), steroid and mycophenolate mofetil (MMF)) has lowered the rate of acute rejection. With the 4-drug combination, however, infection (such as cytomegalovirus (CMV) and BK virus, have become an issue. In the previous study, therefore, we reported high-dose MZR, at 6 mg/kg/day, was effective and safe for kidney transplant patients in conjunction with cyclosporine(CsA), Bas and steroid by a Japanese multicenter study. In this study, we investigated Tacrolimus (Tac) as a CNI and compared with CsA by a Japanese multicenter study.

(Methods) A total of 122 patients were treated with high-dose MZR (6 mg/kg). Fifty one patients were treated with Tac, MZR, Bas, steroid and 71 patients were CsA, MZR, Bas and steroid. CsA was started at a dose of 7 mg/kg to maintain blood levels: 200 ng/ml (CO), 1,200 ng/ml (C2). Tac was started at a dose of 0.2 mg/kg in the target range 8-10 ng/ml (CO). MZR was adjusted to maintain a target CO level of 1-2 [mu]g/ml. ABO incompatible and/or cross match positive patients were excluded.

(Results) Patients and grafts survival rate for 2 years was 100% and 97.3%, respectively. Graft survival of Tac group was 50/51 (98.0%), and CsA graft was 68/71 (95.8%), respectively. The acute rejection rate for 2 years was 13.9%(Tac:13.7%, csA:14.1%). The mean serum creatinine level was 1.55±0.65 mg/dl of CsA group, and 1.33±0.42 mg/dl of Tac at 1 yr, 2.09±2.01 of CsA group, and 1.25±0.45 of Tac group at 2 years. The incidence of CMV disease was 0%, the positive rate of CMV antigenemia 30.3% (CsA:29.6%, Tac:31.4%) and the rate of ganciclovir treatment 8.2%. Bone marrow suppression was seen in 4 patients and liver dysfunction was seen in 5 of patients.

(Conclusion) A regimen of high-dose MZR in combination with CNI (CsA

as well as Tac), Bas, and steroid can establish not only satisfactory immunosuppression but also low rate of CMV infection in vivo.

CITATION INFORMATION: Yoshimura N, Nishimura K, Akioka K, Shimazu M, Nose K, Nishioka T, Nakamura N, Uchida K, Nakatani T, Ushigome H. Excellent Results of Living-Related Renal Transplant Recipients Treated with High-Dose Mizoribine – Comparison of Taclorimus with CsA for Two Years Result by a Japanese Multicenter Study. Am J Transplant. 2016;16 (suppl 3).

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