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Updated: Mar 1, 2026
Robot-Assisted Kidney Transplantation
Published on: July 19, 2021
Beneficial Effects of High-Dose Mizoribine on ABO-Incompatible Living-Related Kidney Transplantation: Two-Year
S Harada1, T Nakamura1, H Ushigome1
1Department of Organ Transplant Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Background:
Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study.
Methods:
A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0-9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8-10 ng/mL (C0), 100 ng-h/mL (AUC 0-9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100-200 mg/body) was administrated on day -14 and day -7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 μg/mL.
Results:
Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively.
Conclusions:
A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.
Insights
High-dose Mizoribine (MZ) with a calcineurin inhibitor effectively prevented cytomegalovirus (CMV) events in ABO-incompatible kidney transplants. This combination therapy demonstrated safety and efficacy in Japanese patients undergoing living-related kidney transplantation (LKT).
Area of Science:
- Nephrology and Immunology
- Transplantation Medicine
- Pharmacology
Background:
- Mizoribine (MZ) is an immunosuppressive agent with limited efficacy at standard doses (up to 3 mg/kg/d).
- Previous studies indicated high-dose MZ (6 mg/kg/d) combined with calcineurin inhibitors (CNIs) may reduce cytomegalovirus (CMV)-related events in ABO-incompatible living-related kidney transplantation (ABO-i LKT).
- This study further investigates the efficacy and safety of high-dose MZ with a CNI in ABO-i LKT recipients.
Purpose of the Study:
- To evaluate the effectiveness and safety of a high-dose Mizoribine (MZ) regimen in patients undergoing ABO-incompatible living-related kidney transplantation (ABO-i LKT).
- To assess the impact of this regimen on cytomegalovirus (CMV)-related events and overall transplant outcomes.
Main Methods:
- A total of 37 patients received high-dose MZ (6 mg/kg/d) along with a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids.
- Specific dosing and target blood levels were maintained for CsA, Tac, and MZ.
- Basiliximab and rituximab were administered peri-transplant, and MZ levels were adjusted to maintain target C0 levels.
Main Results:
- Two-year patient and graft survival rates were high (100% in CsA group, 93.3% in Tac group).
- The incidence of CMV disease was 0% in both groups, although CMV antigenemia rates varied (50.0% CsA vs. 26.7% Tac).
- No significant differences were observed in acute rejection rates, serum creatinine levels, or serum uric acid levels between the CsA and Tac groups at two years.
Conclusions:
- A high-dose Mizoribine (MZ) regimen, combined with a calcineurin inhibitor (CsA or Tac), basiliximab, rituximab, and steroids, is effective and safe for ABO-incompatible living-related kidney transplantation (ABO-i LKT).
- This immunosuppressive strategy significantly reduces the frequency of CMV-related events in this high-risk transplant population.
- The regimen supports favorable long-term graft and patient survival.
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