Background: Measurement of 2-hour Mycophenolic Acid Area-Under-Cure (MPA AUC) has been shown to allow accurate dosing of MMF for therapeutic efficacy. While inadequate MMF administration is associated with both increased expression of anti-donor HLA antibodies (DSA) and irreversible graft dysfunction, over-suppression with MMF is associated with an increased risk of opportunistic infections. Immunocompetence declines with age, and increasing patient age is an independent risk factor for opportunistic infections. This study was undertaken to determine if MMF demonstrates different therapeutic dosing thresholds among different age groups. Methods: This is a retrospective analysis of all renal allograft recipients who underwent MPA AUC testing between April 2010 and October 2012. Patients were assessed for age, current MMF dose at time of testing and AUC results. Mean AUC per MMF dose regimen was assessed independently of patient age by regression analysis. Patients were then age-stratified in 10-year intervals, and minimum MMF dose sufficient to reach therapeutic AUC threshold (>60) was assessed. Mean MMF doses (in mg/day) were expressed as Mean ± SEM. ANOVA and Tukey’s Test were used to analyze statistical significance between age groups. Results: MPA AUC testing was performed on 224 patients (ages 20-80), generating 446 MPA AUC values. A minimum MMF dose of 1500m/d was required to reach therapeutic threshold among all recipients. Among age-stratified recipients, MPA AUC-threshold MMF dose tended to decrease progressively with increasing age, with statistical significance observed between the youngest cohort (age 20-29; 2429 ± 277), and the oldest (>70years; 1646 ± 118).

Discussion: Reductions in MMF dose regimen below 1500 mg/d may not provide adequate protection of renal allografts. Increasing patient age was a significant determinant of MMF dose required to reach therapeutic AUC efficacy threshold. The use of AUC testing is a critical tool in managing elderly transplant recipients, establishing an MMF dosage regimen that will prevent both antibody-mediated allograft injury and immunosuppressant-induced opportunistic infections.

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