BACKGROUND Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used in lupus nephritis treatment. Therapeutic drug monitoring of adults suggests that area under the concentration-time curve (AUC) of MPA (MPA-AUC) is associated with clinical outcomes, but childhood data are scarce. METHODS Retrospective study of 27 children with biopsy-proven lupus nephritis treated with MMF between 2008 and 2016. In 25 children, MPA-AUC was performed within 6 months after kidney biopsy and MMF initiation. Treatment response at 6 months was defined as normal or improved GFR by 25% compared with baseline, 50% reduction of proteinuria to < 0.5 g/day or 50 mg/mmol, and no hematuria. RESULTS A total of 62 MPA-AUC were analyzed in 27 patients. Overall median was 44 mg h/L (interquartile range [IQR] 33-54). Individual dose adaptation was required in 32 cases (52%) to achieve target AUC of 30-60 mg h/L. At 6 months, 14/25 patients were defined as responders (56%, median MPA-AUC 49 mg h/L (40-59)) and 11/25 as non-responders (44%, 29 mg h/L (24-38)). Patients with MPA-AUC levels > 45, 30-45, and < 30 mg h/L had 6-month response rates of 89% (8/9), 60% (6/10), and 0% (0/6), respectively. In a logistic regression model adjusted for age, sex, lupus nephritis classification, and time since MMF initiation, an MPA-AUC > 45 mg h/L was significantly associated with therapeutic response (OR 3.6, 95% CI 2.4-9.5, p = 0.03). CONCLUSIONS Therapeutic drug monitoring leading to individualized dosing may improve efficacy of MMF. MPA-AUC > 45 mg h/L is associated with better response rate and may be considered as a target value in pediatric lupus nephritis.

中文翻译：

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浓度-时间曲线下的霉酚酸面积与儿童期狼疮性肾炎的治疗反应有关。

背景技术霉酚酸(MPA)是霉酚酸酯(MMF)的活性化合物，广泛用于狼疮性肾炎的治疗。成人治疗药物监测表明 MPA 的浓度-时间曲线 (AUC) 下面积 (MPA-AUC) 与临床结果相关，但儿童期数据很少。方法 回顾性研究 27 名 2008 年至 2016 年间接受 MMF 治疗的经活检证实的狼疮性肾炎儿童。在 25 名儿童中，在肾活检和 MMF 启动后 6 个月内进行 MPA-AUC。6 个月时的治疗反应定义为 GFR 与基线相比正常或改善 25%，蛋白尿减少 50% 至 < 0.5 g/天或 50 mg/mmol，并且没有血尿。结果 共分析了 27 名患者的 62 MPA-AUC。总体中位数为 44 mg h/L（四分位距 [IQR] 33-54）。32 例 (52%) 需要个体剂量调整才能达到 30-60 mg h/L 的目标 AUC。在 6 个月时，14/25 名患者被定义为有反应者（56%，中位 MPA-AUC 49 mg h/L (40-59)）和 11/25 被定义为无反应者（44%，29 mg h/L（24 -38))。MPA-AUC 水平 > 45、30-45 和 < 30 mg h/L 的患者的 6 个月反应率为 89% (8/9)、60% (6/10) 和 0% (0/6) ）， 分别。在根据年龄、性别、狼疮性肾炎分类和 MMF 开始时间调整的逻辑回归模型中，MPA-AUC > 45 mg h/L 与治疗反应显着相关（OR 3.6，95% CI 2.4-9.5，p = 0.03）。结论 导致个体化给药的治疗药物监测可能会提高 MMF 的疗效。MPA-AUC >