Safety and Efficacy of a Preemptive Mycophenolate Mofetil Dose Reduction Strategy in Kidney Transplant Recipients.

Abstract

Background: There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of allograft rejection with that of infections and malignancy. At our center, KTRs are managed with either a "preemptive" dose reduction strategy, where the MMF dose is reduced after the first year before the development of adverse events, or with a "reactive" dosing strategy, where they are maintained on the same MMF dose and only reduced if they develop an adverse event. We hypothesized that a preemptive MMF dosing strategy after the first year of transplantation is associated with decreased infections without increasing alloimmune complications.

Methods: We conducted a retrospective cohort study of all KTRs receiving MMF from January 1, 2015, to December 31, 2020. The primary outcome was the incidence of infections requiring hospitalization.

Results: One hundred forty-two KTRs met the inclusion criteria, of whom 44 (31%) were in the preemptive group and 98 (69%) were in the reactive group. The median follow-up was 4 y (interquartile range, 3.8-4.0). Multivariable analysis showed that a preemptive MMF dose reduction strategy was associated with a lower risk of infections requiring hospitalization (adjusted hazard ratio = 0.39; 95% confidence interval, 0.16-0.92). There was no difference in graft loss, rejection, or estimated glomerular filtration rate slope.

Conclusions: Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection. Randomized clinical trials are needed to confirm these findings.