2023年国际儿科肾脏病学会推荐的用于评估霉酚酸暴露的有限治疗药物监测公式的临床适用性

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

作者信息

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

机构信息

University of Western Ontario, London, ON, Canada.

Division of Nephrology, Department of Pediatrics, Western University, 800 Commissioners Road East, London, ON, N6A5W9, Canada.

出版信息

Pediatr Nephrol. 2025 Jun;40(6):1965-1973. doi: 10.1007/s00467-025-06657-w. Epub 2025 Jan 30.

DOI:10.1007/s00467-025-06657-w

PMID:39883131

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 (R 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 (R 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.

摘要

背景

2023年国际儿科肾脏病协会（IPNA）指南建议对小儿肾病综合征进行12小时霉酚酸（MPA）曲线下面积（AUC）评估，且霉酚酸酯（MMF）的最佳治疗反应为MPA AUC＞50mg·h/L。IPNA指南认可了基于三点MPA测量值的两个有限AUC公式来预测12小时MPA AUC。这两个有限AUC公式的相对性能尚未经过测试。

方法

我们分析了122例稳定肾移植受者的156个MPA AUC，使用IPNA推荐的三点公式1和公式2预测12小时AUC（用梯形法则分析10个MPA测量值）。

结果

三点公式1和公式2将69%和60%的有限MPA AUC分类为＞50mg·h/L（差异8.90%，p = 0.10）。三点公式1和公式2与12小时AUC的相关性相似（R分别为0.72和0.71），并且在预测12小时AUC＞50mg·h/L时显示出相同的ROC曲线下面积（AUROC）（AUROC分别为0.82，95%CI 0.75，0.88和0.80，95%CI 0.73, 0.86；p = 0.53）。固定的MMF剂量和MPA C0水平与12小时AUC的相关性相对较弱（R分别为0.16和0.43）。与三点公式相比，四点MPA公式改善了12小时AUC预测。在所有C0阈值中，C0＞3.5mg/L对12小时AUC＞50mg·h/L的预测最佳（AUROC 0.74，95%CI 0.66，0.80）。