Initial mycophenolate dose in tacrolimus treated renal transplant recipients, a cohort study comparing leukopaenia, rejection and long-term graft function

Dave, Vatsa; Polkinghorne, Kevan R.; Leong, Khai Gene; Kanellis, John; Mulley, William R.

doi:10.1038/s41598-020-76379-6

Cited by 11 publications

(18 citation statements)

References 30 publications

(52 reference statements)

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“…[23,24] In patients from the lower dose group was not necessary a greater reduction, despite the fact that those with standard dose experience a significant reduction in MMF doses however none were lower than 1.5g in either group. However, in contrast to findings from a retrospective analysis reported by Dave V et al, [25] we did not find that an initial low dose of MMF was associated with an increase in the incidence of AR, although the population studied in this analysis was different (45% deceased donor recipients, 17% with panel reactive antibodies (PRA) higher 20% and ABO blood group incompatible in 22%. We only evaluate survival-free of AR during followup (12 months), suggesting that the initial dose of 1.5g of MMF does not lead to increased risk of AR a short-term in our population.…”

Section: Discussioncontrasting

confidence: 99%

“…Immunosuppression reduction is a clinical challenge, our experience in this field is based to steroid reduction [3,4,20], however clinical protocols in our setting allows to consider other pharmacological reductions i.e. MMF, there is an international evidence in MMF reduction with controversial [18,19,[21][22][23][24][25] results, in Latin America there is not experience regarding this topic; Nevertheless, since the early post-transplant stages could considered the relatively low incidence of AR under the immunosuppressive regimens with TAC especially in low immunological risk patients clinicians find themselves having to reduce the doses of MMF, empirically, due to the presence of adverse effects. Thus, an actual tendency in our setting is to initiate, in the immediate post-transplant period, a dose of 1.5g/day.…”

Section: Introductionmentioning

confidence: 99%

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Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Andrade‐Sierra

Hernández-Reyes

Rojas‐Campos

et al. 2022

Preprint

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Background. The evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) in renal transplant (RT) is still limited but maintaining the dose of less than 2g could result in worse clinical outcomes in terms of acute rejection (AR). Research Question: This study aim was to determine the association between AR, infectious and non-infectious complications after RT with the dose of 1.5g vs. 2g of MMF. Design. A prospective cohort was performed with a 12-month follow-up in recipients of RT from living donors with low doses of MMF (1.5 g/day) or use of standard dosage (2 g/day). The association between adverse effects and complications and doses of MMF were examined in Cox proportional hazard models and survival free of AR, infectious diseases, and non-infectious complications was evaluated by the Kaplan-Meier test. Results. At the end of the follow-up, the incidence of infectious diseases was 52% vs. 50% (p=0.71) and AR was 5% vs. 5% (p=0.86), respectively. Survival free of GI complications requiring medical attention was higher in the low dose group compared to the standard dose (88% vs. 45%, respectively; p<0.001). Discussion. The use of 1.5 g/day of MMF is safe in Mexican population with RT from living donors without increasing the risk of AR, and it confers a reduction of adverse events.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Andrade‐Sierra

Hernández-Reyes

Rojas‐Campos

et al. 2022

Preprint

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“…Therefore, as corticosteroids are weaned over time, the MMF exposure increases, potentially explaining the divergence in neutropenia curves after the first month post‐HT. Additionally, the higher corticosteroid dosages early post‐HT drive neutrophil margination and likely mask the effect of MMF dosing on ANC in the first month post‐HT, which is consistent with data reported in kidney transplant patients 21 …”

Section: Discussionsupporting

confidence: 86%

“…Additionally, the higher corticosteroid dosages early post-HT drive neutrophil margination and likely mask the effect of MMF dosing on ANC in the first month post-HT, which is consistent with data reported in kidney transplant patients. 21 The MMF-HD group also exhibited prolonged duration of neutropenia despite similar baseline leukocyte count and G-CSF use.…”

Section: F I G U R Ementioning

confidence: 90%

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

et al. 2022

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Study Objective: Mycophenolate mofetil (MMF) is the gold-standard immunosuppressive agent in heart transplantation (HT), but dose-dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria βd-glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high-dose, HD] versus 1 g q12 [low-dose, LD] and explore the association between neutropenia and GUS. Measurements:We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post-HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing.Main Results: A total of 168 patients (120 MMF-HD, 48 MMF-LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 days. Freedom from neutropenia was lower in MMF-HD compared with MMF-LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10-96] days, while high-grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9-89] days. Freedom from ACR was similar between groups. MMF-LD was associated with more high-grade ACR (hazard ratio [HR] 3.47, 95% confidence interval[CI] 1.09-11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29-1.00, p = 0.05) between 1 and 6 months. GUS-producing bacteria were more abundant in neutropenic patients.Conclusions: MMF-LD was associated with higher rates of early high-grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post-HT.

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“…Cyclosporine A and tacrolimus have similar reaction mechanisms. Some scholars have found in vivo experiments that it has a better effect on liver and kidney transplantation [ 28 ]. Although the two CNIs suppress the immune system through similar mechanisms, differences in their side effects can be observed.…”

Section: Discussionmentioning

confidence: 99%

Effect of MMF Immunosuppression Based on CNI Reduction on CNI-Related Renal Damage after Lung Transplantation

Tang

Wang

Xue

et al. 2022

Journal of Healthcare Engineering

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In this paper, numerous effects of immunosuppressive regimen of mycophenolate mofetil (MMF) on CNI-related renal damage after lung transplantation are evaluated thoroughly. For this purpose, 110 lung transplant recipients who were treated in our hospital from March 2016 to January 2018 were randomly selected. All patients took prednisone acetate tablets or rapamycin at the same time or not at the same time. MMF is 1 g every time, twice a day, and adjusted according to the re-examination. According to the different drugs taken by 110 patients, they were divided into cyclosporine A group and tacrolimus group. Among them, 92 patients in cyclosporine A group took cyclosporine A; 18 patients in tacrolimus group took tacrolimus. The clinical data of age and gender of the two groups were collected, To observe and compare the occurrence of CNI-related renal damage in lung transplant recipients and different immunosuppressants. The CNI dosage of tacrolimus group and cyclosporine A group was compared before and after MMF. The changes of serum creatinine level and serum creatinine clearance rate were measured before MMF administration and 30, 60, and 90 days after MMF administration, to observe the complications of CNI-related renal damage after lung transplantation. Experimental results showed that there were 16 cases (14.55%) of CNI-related renal damage in lung transplant recipients and different immunosuppressants, including 10 cases (11.36%) in males, 6 cases (27.27%) in females, 11 cases (12.09%) in tacrolimus group, and 5 cases (26.32%) in cyclosporine A group. There was no significant difference between the two groups ( P > 0.05 ). Compared with MMF before and after administration, CNI dosage of cyclosporine A group and tacrolimus group decreased significantly ( P < 0.01 ). Compared with MMF before administration, serum creatinine level decreased and serum creatinine clearance rate increased significantly ( P < 0.05 ). In the follow-up, 16 patients with CNI-related renal damage were found to be immune rejection before the adjustment of immunosuppression program, no complications such as immune rejection, myelosuppression, and infection occurred within 15 months after the adjustment of immunosuppression program, blood glucose increased in 3 patients within 2 years after operation, blood lipid increased in 1 patient, urea increased in 1 patient, and uric acid increased in 1 patient. MMF immunosuppressive therapy based on CNI reduction is a safe and effective immunosuppressive therapy, which can significantly reduce immune rejection, improve renal function, and play an important role in improving CNI-related renal damage after lung transplantation.

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Initial mycophenolate dose in tacrolimus treated renal transplant recipients, a cohort study comparing leukopaenia, rejection and long-term graft function

Cited by 11 publications

References 30 publications

Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

Effect of MMF Immunosuppression Based on CNI Reduction on CNI-Related Renal Damage after Lung Transplantation

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