Optimizing mycophenolic acid exposure for reduced relapse risk in paediatric nephrotic syndrome: An observational cohort study.

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

British journal of clinical pharmacology Pub Date : 2025-10-08 DOI:10.1002/bcp.70307

Yiting Cai, Baojing Liu, Lizhi Chen, Lu Zhang, Kejing Tang, Xiaoyun Jiang, Pan Chen

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引用次数: 0

Abstract

Aims: Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC_0-12h) for relapse prevention during maintenance therapy.

Methods: In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).

Results: Lower MPA AUC_0-12h levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC_0-12h as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.

Conclusions: Maintaining MPA AUC_0-12h ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.

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优化霉酚酸暴露降低儿科肾病综合征复发风险：一项观察性队列研究。

目的：霉酚酸（MPA）可有效减少小儿肾病综合征（NS）的复发，但其药代动力学变异性阻碍了最佳剂量。本研究旨在确定维持治疗期间MPA面积浓度-时间曲线下（AUC0-12h）预防复发的风险参考值。方法：在这项回顾性队列研究中，纳入了89例接受MPA治疗的儿科NS患者。通过二元logistic回归评估影响复发的因素。采用受试者工作特征（ROC）曲线确定最佳截止阈值，Kaplan-Meier和Cox回归分析评估无复发生存期（RFS）。结果：低MPA AUC0-12h水平与复发有较强的相关性(复发组：31.49 vs.非复发组：36.48 μg/h/mL， P 0-12h为保护因素（优势比[OR] = 0.93, 95%可信区间[CI]: 0.88-0.99）。ROC分析确定31.51 μg/h/mL为最佳风险参考值（敏感性为87.5%，特异性为51.02%）。Cox回归进一步证实亚阈暴露为独立复发风险（风险比[HR] = 0.24, 95% CI: 0.14-0.43， P）。结论：维持MPA AUC0-12h≥31.51 μg/h/mL可显著降低小儿NS复发风险。个体化霉酚酸酯（MMF）剂量指导下的治疗药物监测是优化结果的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of clinical pharmacology 医学-药学

CiteScore

6.30

自引率

8.80%

发文量

419

审稿时长

1 months

期刊介绍： Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.