Clinical applicability of 2023 International Pediatric Nephrology Association recommended limited therapeutic drug monitoring formulae to assess mycophenolic acid exposure.

IF 2.6 3区医学 Q1 PEDIATRICS Pediatric Nephrology Pub Date : 2025-06-01 Epub Date: 2025-01-30 DOI:10.1007/s00467-025-06657-w

Ajay P Sharma, Mara Medeiros, Shamim Norozi, Alethia Paulina Monserrat Guzmán-Núñez, Guido Filler

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Abstract

Background: The 2023 IPNA guidelines recommended a 12-h mycophenolic acid (MPA) area under the curve (AUC) estimation for managing pediatric nephrotic syndrome and MPA AUC > 50 mg * h/L for an optimal therapeutic response to mycophenolate mofetil (MMF). The IPNA guidelines endorsed two limited AUC formulae based on three-point MPA measurements to predict 12-h MPA AUC. The relative performance of these two limited AUC formulae has not been tested.

Methods: We analyzed 156 MPA AUCs from 122 stable kidney transplant recipients to predict the 12-h AUC (10 MPA measurements analyzed with trapezoid rule) using the IPNA-recommended three-point Formula 1 and Formula 2.

Results: Three-point Formula 1 and Formula 2 classified 69% and 60% limited MPA AUCs as > 50 mg * h/L (difference 8.90%, p = 0.10). Three-point Formula 1 and Formula 2 demonstrated a similar association with 12-h AUC (R² 0.72 vs. 0.71) and exhibited identical areas under ROC (AUROC) for predicting 12-h AUC > 50 mg * h/L (AUROC 0.82, 95% CI 0.75, 0.88 vs. 0.80, 95% CI 0.73, 0.86; p = 0.53). Fixed MMF dose and MPA C0 level showed a relatively weaker association (R² 0.16 and 0.43) with 12-h AUC. Four-point MPA formulae improved the prediction of 12-h AUC compared to the three-point formulae. Among all C0 thresholds, C0 > 3.5 mg/L demonstrated the best prediction of 12-h AUC > 50 mg * h/L (AUROC 0.74, 95% CI 0.66, 0.80).

Conclusions: IPNA recommended limited AUC formulae perform equivalently and improve upon MMF dose and C0 level to predict 12-h MPA AUC.

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2023年国际儿科肾脏病学会推荐有限的治疗药物监测配方来评估霉酚酸暴露的临床适用性。

背景：2023年IPNA指南推荐12小时霉酚酸（MPA）曲线下面积（AUC）估计用于治疗儿童肾病综合征，MPA AUC低于50 mg * h/L用于霉酚酸酯（MMF）的最佳治疗效果。IPNA指南采用了两个基于三点MPA测量的有限AUC公式来预测12小时MPA AUC。这两种有限AUC公式的相对性能尚未进行测试。方法：采用ipna推荐的三点公式1和公式2，对122例稳定肾移植受者的156 MPA AUC进行分析，预测12小时AUC （10 MPA测量值采用梯形定则分析）。结果：三点式(1)和三点式(2)将69%和60%的限定MPA AUCs划分为> 50 mg * h/L（差异8.90%,p = 0.10）。三点式1和式2与12小时AUC有相似的相关性（R2 0.72 vs. 0.71），在ROC （AUROC）下预测12小时AUC的面积相同(AUROC 0.82, 95% CI 0.75, 0.88 vs. 0.80, 95% CI 0.73, 0.86；p = 0.53)。固定MMF剂量和MPA C0水平与12 h AUC的相关性相对较弱（R2分别为0.16和0.43）。与三点MPA公式相比，四点MPA公式提高了对12 h AUC的预测。在所有C0阈值中，C0 > 3.5 mg/L对12 h AUC > 50 mg * h/L的预测效果最好（AUROC为0.74,95% CI为0.66,0.80）。结论：IPNA推荐的有限AUC处方与MMF剂量和C0水平预测12 h MPA AUC的效果相当，且有所提高。

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来源期刊

Pediatric Nephrology 医学-泌尿学与肾脏学

CiteScore

4.70

自引率

20.00%

发文量

465

审稿时长

1 months

期刊介绍： International Pediatric Nephrology Association Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.