Establishing Mycophenolate Therapeutic Drug Monitoring Targets in Childhood Nephrotic Syndrome

Authors

• Magdalena Riedl Khursigara, The Hospital for Sick Children
• Cal H. Robinson, The Hospital for Sick Children
• Erin Chung, The Hospital for Sick Children
• Winnie Seto, The Hospital for Sick Children
• Diana Hamdan, Kansas City University
• Junhee Hong, The Hospital for Sick Children
• Valentina Bruno, The Hospital for Sick Children
• Nowrin Aman, The Hospital for Sick Children
• Tonny H.M. Banh, The Hospital for Sick Children
• Judy Truong, The Hospital for Sick Children
• Josefina Brooke, The Hospital for Sick Children
• Vaneet Dhillon, The Hospital for Sick Children
• Mackenzie Garner, The Hospital for Sick Children
• Christoph Licht, The Hospital for Sick Children
• Ashlene McKay, The Hospital for Sick Children
• Damien Noone, Stollery Children’s Hospital
• Rachel Pearl, The Hospital for Sick Children
• Seetha Radhakrishnan, The Hospital for Sick Children
• Keisha Rasool, The Hospital for Sick Children
• Nithiakishna Selvathesan, The Hospital for Sick Children
• Kristen Vanos, The Hospital for Sick Children
• Jovanka Vasilevska-Ristovska, The Hospital for Sick Children
• Rulan S. Parkeh, The Hospital for Sick Children
• James Tjon, The Hospital for Sick Children
• Chia Wei Teoh, The Hospital for Sick Children

Document Type

Article

Publication Title

Kidney International Reports

Abstract

Introduction: Mycophenolic acid (MPA) is a commonly used steroid-sparing immunosuppressant in nephrotic syndrome. Therapeutic drug monitoring (TDM) based on area under the concentration-time curve (AUC) target ranges is not well-established. We aimed to propose exposure TDM targets for MPA in children with nephrotic syndrome when used concomitantly with rituximab.
Methods: We performed a retrospective analysis of children with nephrotic syndrome treated with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). Exposures included MPA-AUC_0-12h, MPA trough concentrations, and MMF equivalent dose. Clinical outcomes included relapse rate, time-to-relapse, and adverse effects. We determined a favorable MPA-AUC_0-12h range, based on time-to-relapse and adverse effects. Poisson regression models with natural splines and receiver operating characteristic curves were used.
Results: A total of 131 MPA-AUC_0-12h measurements were performed among 67 children with frequently relapsing nephrotic syndrome (FRNS). MPA-AUC_0-12h, but not trough concentration or MMF equivalent dose, was strongly correlated with relapse rate and time-to-relapse. A 10 mg h/l increase of MPA-AUC_0-12h was associated with fewer relapses (incidence rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.59– 0.82) and longer time-to-relapse (hazard ratio [HR], 0.77; 95% CI: 0.64–0.92). For relapse rate, the best model fit was achieved using 2 knots at MPA-AUC_0-12h of 41 and 57 mg h/l. Higher MPA-AUC_0-12h, especially $ 60 mg h/l, was associated with increased risk of neutropenia (odds ratio, 1.18 per 10 mg h/l increase; 95% CI, 1.02–1.36). Conclusion: Our findings suggest an initial target MPA-AUC_0-12h between 40 to 60 mg h/l provided a favorable balance between relapse prevention and adverse effects. Further increases of MPA-AUC_0-12h > 60 mg h/l may provide further relapse risk reduction, but should be carefully weighed against neutropenia risk.

DOI

10.1016/j.ekir.2026.107131

Publication Date

12-2026

Keywords

area under the curve, mycophenolic acid, nephrotic syndrome, therapeutic drug monitoring

ISSN

2468-0249

Recommended Citation

Khursigara MR, Robinson CH, Chung E, Seto W, Hamdan D, Hong J, Bruno V, Aman N, Banh TH, Truong J, Brooke J, Dhillon V, Garner M, Licht C, McKay A, Noone D, Pearl R, Radhakrishnan S, Rasool K, Selvathesan N, Vanos K, Vasilevska-Ristovska J, Parkeh RS, Tjon J, Teoh CW. Establishing Mycophenolate Therapeutic Drug Monitoring Targets in Childhood Nephrotic Syndrome. Kidney International Reports. 2026; 11(12). doi: 10.1016/j.ekir.2026.107131.