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

Abstract

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

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

“…[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.…”

“…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.…”

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

“…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 …”

“…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.…”

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

“…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.…”