Dr Sonia Sharma1,2, Dr Joshua Kausman2, Dr David Metz2
1Monash University , Melbourne , Australia , 2Royal Children Hospital , Melbourne , Australia
Biography:
PhD Scholar at Monash University
Honorary Nephrologist at Royal Children Hospital
Previously Consultant Paediatric Nephrologist : Experience in New Delhi, India
Trained Paediatric Nephrologist, FIPNA, FIAPN
Background:
Mycophenolate mofetil is a key maintenance immunosuppressant in kidney transplantation. Controlled MPA dosing using AUC monitoring reduces acute rejection, but clinical application is limited due to complex methods. The trapezoid method, though simple and widely used, lacks published evidence supporting its accuracy. This study aimed to evaluate the predictive performance of 4-point and 6-point trapezoid AUC methods (over 4 hours) compared to Bayesian AUC, the current standard for estimating full AUC and used in trials with improved outcomes.
Methods:
This was a single-center retrospective study using electronic medical record data. AUCs were calculated using 4 & 6-point trapezoid and Bayesian methods, with accuracy assessed via forecasting techniques. Linear and mixed-effects models were used to analyze MPA exposure and clinical factors.
Results:
73 patients (46 males), with a median age 10 years (range 1.3–22) had a follow-up of 52.9 months, included 196 MPA AUC assessments. Median BMI z score and GFR were 0.4 (range -2.2 to 2.7) and 63.4 (range 7.1 to 137.3) ml/min/1.73 m², respectively. The 6-point method showed strong predictive performance: MAPE = 10.09%, MPPE = -0.33%, RMSE = 17.56, and excellent Bland-Altman agreement. In contrast, the 4-point trapezoid method performed poorly. Mean (SD) MPA exposure & dosage were 42.24 (18.47) mg.h/L & 624.61 (180.21) mg/m²/day respectively. A 33% variance in exposure (R² = 0.3244) was associated with normalized dosing. No significant correlation was found with trough levels (R² = 0.27), age, or MMF formulations.
Conclusion:
The 6-point, but not 4-point, trapezoid method demonstrates high accuracy and may offer a clinically useful alternative for monitoring. MPA exposure variability supports long-term AUC monitoring.
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