Renal transplantationImmunosuppressionA Japanese Multicenter Study of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroid in Renal Transplantation (The Fourth Report)
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Study Subjects and Immunosuppression Protocol
The 39 patients aged ≤70 years underwent ABO-compatible or identical kidney transplantation after June 2006 at one of the following 6 institutes: Keio University Hospital, Fujita Health University Hospital, Toho University Omori Medical Center, Kitasato University Hospital, National Defense Medical College Hospital, and University of the Ryukyus Hospital. All patients provided informed consent. The study was approved by the ethics committees of the participating institutes. The
Results
The 39 patients treated with the high-dose MZR immunosuppressive protocol (Table 1) showed an average age of 30.7 years, including 9 aged ≤10 years (25.6%) and 30 aged ≥11 years (74.6%). The patients consisted of 26 males and 13 females, with donor type being living donor in 37 and deceased in 2.
Twelve ARE occurred in 9/39 patients (23.1%). ARE-free survival in children aged ≤10 years tended to be lower than that in those aged ≥11 years (Fig 2). The incidence of ARE correlated with MZR blood
Discussion
Although MMF has decreased early post-transplantation rejection rate, it has increased the incidence of CMV infection. Both the increased incidence of infections with CMV, BK virus, and adenovirus as well as the adverse side effects of diarrhea, abdominal discomfort, and leukopenia have led to a conversion of treatment of some transplant recipients to MZR.3 Although MZR has been used as an immunosuppressive agent in Japan for over 25 years, at standard doses (1–3 mg/kg/d) it is less effective
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Cited by (9)
Comparative Study of Mizoribine and Mycophenolate Mofetil Combined with a Calcineurin Inhibitor-Based Immunosuppressive Regimen in Patients with Alternative Donor Hematopoietic Cell Transplantation
2020, Biology of Blood and Marrow TransplantationCitation Excerpt :Furthermore, the scheme used in this study did not record episodes of diarrhea in the adverse event files because of concerns about not accurately determining the true causes of diarrhea in the HCT setting; another study found that treatment with MZR was associated with fewer episodes of diarrhea compared with treatment with MMF in renal transplantation [11]. Nevertheless, the present study suggests that MZR showed good immunosuppressive as well as antiviral effects in the setting of HCT, which is similar to the results in a series of reports on renal transplantation [11,16-19]. GVHD is the most important immune event that must be overcome in HCT, similar to graft rejection in solid organ transplantation.
Long-term Survival Analysis of Kidney Transplant Recipients Receiving Mizoribine as a Maintenance Immunosuppressant: A Single-Center Study
2019, Transplantation ProceedingsCitation Excerpt :Mizoribine has been shown to have relatively lower pharmacologic efficacy than mycophenolate mofetil (MMF) or azathioprine, both of which inhibit purine synthesis as immunosuppressants [5]. Correspondingly, recent reports have shown that efficacy and safety in kidney transplant can be achieved when MZR is used above the recommended dose [6,7]. It was also reported that high-dose MZR can be effectively and safely used even in ABO-incompatible kidney transplant [8].
Comparative efficacy and safety of mizoribine with mycophenolate mofetil for Asian renal transplantation-A meta-analysis
2014, Clinical BiochemistryCitation Excerpt :Because of the predominant renal metabolism, the dosage of MZR should be adapted to the glomerular filtration rate and MZR plasma trough level to avoid overimmunosuppression and adverse effects. As MZR passes a cell membrane according to the gradient of its concentration, currently, most of the RCTs from Japan are conducted to prove the efficacy and safety of high-dose MZR, distinguishing from the low-dose MZR use previously [10,11]. In this study, we examined whether high-dose MZR (≧ 3 mg/kg/d) was as effective and safe as MMF for patients at a stable phase after renal transplantation.
Dexamethasone Prolongs Cardiac Allograft Survival in a Murine Model Through Myeloid-derived Suppressor Cells
2018, Transplantation ProceedingsCitation Excerpt :Therefore, it appears that Dex suppresses the immune system through MDSCs via different pathways to rapamycin. A variety of immunosuppressant drugs, such as calcineurin inhibitors, mycophenolate mofetil, mizoribine, and steroids, have been used to suppress the immune system in organ transplant recipients through different immunosuppressive pathways [26–28]. Combination therapy with Dex and rapamycin as prophylaxis against graft rejection may benefit transplant recipients because each affects MDSCs through a different immunosuppressive pathway.
Genetic and clinical determinants of mizoribine pharmacokinetics in renal transplant recipients
2021, European Journal of Clinical Pharmacology