Background/Purpose: Mycophenolate mofetil (MMF) is often used to treat lupus nephritis (LN) and extra-renal lupus in children with SLE. Plasma levels of mycophenolic acid (MPA) are used in clinical practice to determine absorption of MMF and compliance.  However, data are equivocal in the use of plasma MPA levels as a measure of efficacy or a predictor of prognosis in pediatric LN patients.  This study was initiated to evaluate the use of MPA levels in routine care of children with LN.

Methods: This is a retrospective study of pediatric LN patients treated with MMF. Data were collected on demographic and disease characteristics, concomitant medications, and treatment outcomes. Complete renal remission (CR) was defined as proteinuria <500mg/24h, and no other clinical manifestations of renal disease. Mid-interval MPA plasma levels were drawn during routine follow-up. Calculated steady-state concentrations can predict plasma MPA levels at peak, trough, or any time during the dosing interval. Steady-state levels of MPA were calculated using basic pharmacokinetics and compared to routine mid-interval plasma MPA levels. Student t-tests were used when appropriate.

Results: We describe 17 patients with pediatric lupus nephritis treated with MMF that have plasma MPA levels available from our cohort. The mean duration of SLE was 5 years, and LN was 3.3 years. Ten LN patients were in CR at the time of this study, 5 had mixed proliferative/membranous nephritis and 5 had proliferative disease alone. All 7 patients not in CR had some component of membranous LN. MMF was dosed at 600mg/m²/dose for all patients. The mean dose of corticosteroids was 23.75mg prednisone equivalent/day in patients in CR compared with 62.5mg prednisone equivalent/day in patients with persistent disease (p=0.06). The mean mid-interval levels of MPA were 1.69 ug/ml (range <0.5 to 8 ug/ml) in patients in CR and 2.04 ug/ml (range <0.5 to 6 ug/ml) in patients with persistent active disease (p=NS). Of note, 3 patients in each group had undetectable MPA levels. Based on dose, the calculated mid-interval steady-state level was 13.62 ± 3.67 mg*h/L and did not reflect the observed mid-interval levels.

Conclusion: This is the first study to investigate the correlation between mid-interval levels of MPA and predicted steady-state serum levels in patients with lupus nephritis.  Our data suggest a large inter-individual variability but also clearly raise concerns about compliance with MMF regimens and emphasize the need to more precisely monitor MPA levels with peak, trough, and area-under-the-curve, as well as the need to discuss with patients and families the reason(s) for non-compliance.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/monitoring-of-mid-interval-plasma-levels-of-mycophenolic-acid-in-pediatric-lupus-nephritis-patients/