Yoshimura N, Ushigome H, Nobori S, Suzuki T, Sakai K, Koshino K, Nakamura T, Nakao T, Harada S, Ito T
Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Transplant Proc. 2014;46(2):391-4. doi: 10.1016/j.transproceed.2013.10.061.
Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years.
From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) .
The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups.
A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.
咪唑立宾（MZR）在日本已被开发用作免疫抑制剂，但在剂量高达3mg/kg/d时免疫抑制作用较弱。我们之前报道，在一项为期1年的研究中，高剂量MZR（6mg/kg/d）与环孢素（CsA）或他克莫司（FK）、抗CD20和抗CD25单克隆抗体以及皮质类固醇联合使用，不进行脾切除术，对ABO血型不相容（ABO-i）活体供肾移植（LDKT）患者是有效且安全的。因此，我们对这些患者进行了3年的观察。
2007年至2010年，我们遇到24例未进行脾切除术使用抗CD20和抗CD25单克隆抗体的ABO-i LDKT病例。移植前免疫抑制方案包括两剂抗CD20抗体、霉酚酸酯（MMF，25mg/kg/d）、泼尼松龙、钙调神经磷酸酶抑制剂（CNI；CsA 7mg/kg或FK 0.2mg/kg）和两剂抗CD25抗体。根据抗体滴度，在LDKT前进行血浆置换清除抗体，次数可达数次。移植后方案包括用高剂量MZR（6mg/kg/d）替代MMF（MZR组，N = 12）。
MZR组和MMF组的3年移植肾存活率分别为91.7%和100%。MZR组和MMF组的血清肌酐水平在1年时分别为1.44mg/dL和1.31mg/dL，2年时分别为1.55mg/dL和1.41mg/dL，3年时分别为1.51mg/dL和1.48mg/dL（无显著差异[NS]）。MZR组未显示血清尿酸值升高率更高。在第三年，MZR组接受抗尿酸药物治疗的患者百分比为42.5%（5/12），MMF组为50%（6/12）（P = NS）。两组在第二年和第三年均未观察到严重感染，如巨细胞病毒、带状疱疹。
在ABO-i肾移植中，包括CNI（CsA或FK）、类固醇以及抗CD20和抗CD25抗体且不进行脾切除术的高剂量MZR方案是有效且安全的。
