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Published on: November 8, 2015
Low dose of mycophenolate mofetil is enough in desensitized kidney transplantation using rituximab
Chung Hee Baek1, Hyosang Kim2, Hoon Yu3
1Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. bch393@naver.com.
Background:
Rituximab is widely used in kidney transplantation. However, it is not clear whether the conventional doses of maintenance immunosuppressant in rituximab-treated kidney transplantation (KT) are appropriate. In our previous study, decreasing mycophenolate mofetil (MMF) dose due to infection did not increase the incidence of rejection or graft failure. Based on these experiences, we developed a new protocol with a lower dose of MMF and studied its clinical outcomes in rituximab-treated KT.
Methods:
We enrolled all patients who underwent ABO-incompatible or human leukocyte antigen (HLA)-sensitized living donor KT with the new immunosuppressant protocol after preconditioning with rituximab, but without splenectomy from November 2011 to May 2013. Seventy-two patients (group 1) were consecutively enrolled in this study and followed until November 2013. Patients from our previous study served as control groups. Sixty-seven patients received KT using rituximab with a conventional dose of MMF (group 2), and 87 patients received ABO compatible KT without need for rituximab (group 3). Clinical outcomes, including rejection, infection, and graft survival, were compared between the groups. The χ (2) test and Fisher's exact test were used for categorical variables, the Student's t-test and Mann-Whitney U test were used for continuous variables, and a log-rank test was used for mortality analysis.
Results:
Doses of postoperative MMF (g/day) were lower in group 1 than in the other groups (1.03 ± 0.19, 1.48 ± 0.34 and 1.48 ± 0.32 g/day at 1 week, p < 0.001). Infectious complications occurred more often in groups with conventional MMF doses (group 2 and 3) than in group 1 (16.7 vs. 37.3 %, p = 0.007 and 16.7 vs. 34.5 %, p = 0.012, respectively). Notably, group 1 showed a lower incidence of cytomegalovirus infection than group 2. However, reduction in MMF dose did not increase the incidence of acute rejection (4.2, 4.5 and 10.3 %). Only one graft failure occurred in group 2 due to vessel kinking after operation. There were no significant differences in the incidence of malignancy and mortality between groups.
Conclusions:
A low MMF dose reduces infection without increasing rejection or graft loss and it may be appropriate to reduce the dose of MMF for rituximab-treated KT patients.
Insights
Reducing mycophenolate mofetil (MMF) dosage in kidney transplant (KT) patients treated with rituximab lowers infection rates. This lower MMF dose did not increase rejection or graft loss, suggesting a potentially safer immunosuppression strategy.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation immunology
Background:
- Rituximab is a common treatment in kidney transplantation (KT).
- Optimal maintenance immunosuppression doses in rituximab-treated KT patients remain unclear.
- Previous studies indicated reduced mycophenolate mofetil (MMF) doses did not increase rejection or graft failure.
Purpose of the Study:
- To evaluate the clinical outcomes of a new immunosuppression protocol using a lower MMF dose in rituximab-treated KT patients.
- To compare infection, rejection, and graft survival rates between patients on the new protocol and those on conventional MMF doses.
Main Methods:
- A prospective study enrolled 72 patients undergoing ABO-incompatible or HLA-sensitized living donor KT with rituximab and a reduced MMF dose (group 1).
- Outcomes were compared to historical control groups: 67 patients on rituximab with conventional MMF (group 2) and 87 patients without rituximab (group 3).
- Statistical analyses included chi-squared, Fisher's exact, Student's t-test, Mann-Whitney U, and log-rank tests.
Main Results:
- Group 1 (low MMF) had significantly lower MMF doses (1.03 g/day) compared to groups 2 and 3 (1.48 g/day).
- Infectious complications were less frequent in group 1 (16.7%) versus groups 2 (37.3%) and 3 (34.5%).
- Incidence of acute rejection, graft failure, malignancy, and mortality were similar across groups, with a notable reduction in cytomegalovirus infections in group 1.
Conclusions:
- A reduced MMF dose in rituximab-treated KT patients effectively lowers infection rates.
- This strategy appears safe, as it does not increase the risk of rejection or graft loss.
- Lowering MMF dosage may be an appropriate adjustment for rituximab-based immunosuppression in KT.
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