Lim Yinru, Lyall Hermione, Foster Caroline
The Family Clinic, Department of Paediatrics, Imperial College Healthcare NHS Trust, London, UK,
Clin Drug Investig. 2015 May;35(5):327-33. doi: 10.1007/s40261-015-0287-5.
In 2012, tenofovir disoproxil fumarate (TDF) was approved for use in children over 2 years of age at a dose of 8 mg/kg/day, and is the WHO recommended first-line therapy for children over 10 years of age or 35 kg in weight, at 300 mg daily. Whilst postmarketing experience of paediatric TDF is limited, prior off-licence use has occurred at our centre due to its tolerability, efficacy and resistance profiles. In this article we describe a single-centre experience of TDF nephrotoxicity in children aged <16 years.
We conducted a retrospective case-note audit of children with perinatally-acquired HIV who ever received TDF-based antiretroviral therapy.
From 2001 to December 2013, 70 children [39 (56 %) females] ever received TDF. Median age at the start of TDF treatment was 12 years (interquartile range 10-14). Seven (10 %) children developed asymptomatic renal tubular leak with associated hypophosphataemia (3) and hypokalaemia (1), all resulting in TDF withdrawal and biochemical resolution. Comparison of the nephrotoxic group versus the rest of the cohort showed no significant differences for age, sex, antiretroviral regimen or CD4 count. Lower weight (p = 0.05) and initial dose of TDF received (p = 0.0048) were significantly associated with TDF-induced nephrotoxicity: median dose of TDF (7.8 mg/kg/day) compared with the remainder of the cohort (6.5 mg/kg/day). Concurrent use of protease inhibitors (PIs) with TDF may be a contributing factor to the development of nephrotoxicity (odds ratio 6; 95 % CI 0.7-54; p = 0.111).
Although all children with TDF-associated nephrotoxicity had biochemical resolution on drug withdrawal, renal monitoring of children receiving TDF is important, especially with the co-administration of PIs. Postmarketing surveillance is essential in the paediatric setting.
2012年，富马酸替诺福韦二吡呋酯（TDF）被批准用于2岁以上儿童，剂量为8毫克/千克/天，是世界卫生组织推荐的10岁以上或体重35千克以上儿童的一线治疗药物，每日剂量为300毫克。虽然儿科TDF的上市后经验有限，但由于其耐受性、疗效和耐药性特征，我们中心此前曾有过非许可使用的情况。在本文中，我们描述了16岁以下儿童TDF肾毒性的单中心经验。
我们对曾接受基于TDF的抗逆转录病毒治疗的围产期感染艾滋病毒儿童进行了回顾性病例记录审核。
从2001年到2013年12月，70名儿童[39名（56%）女性]曾接受TDF治疗。开始TDF治疗时的中位年龄为12岁（四分位间距10 - 14岁）。7名（10%）儿童出现无症状肾小管渗漏，并伴有低磷血症（3例）和低钾血症（1例），所有这些都导致TDF停药且生化指标恢复正常。肾毒性组与队列其他儿童在年龄、性别、抗逆转录病毒治疗方案或CD4细胞计数方面无显著差异。较低体重（p = 0.05）和最初接受的TDF剂量（p = 0.0048）与TDF诱导的肾毒性显著相关：TDF的中位剂量为（7.8毫克/千克/天），而队列其他儿童为（6.5毫克/千克/天）。TDF与蛋白酶抑制剂（PIs）同时使用可能是肾毒性发生的一个促成因素（比值比6；95%置信区间0.7 - 54；p = 0.111）。
虽然所有与TDF相关的肾毒性儿童在停药后生化指标均恢复正常，但对接受TDF治疗的儿童进行肾脏监测很重要，尤其是在同时使用PIs的情况下。在儿科环境中，上市后监测至关重要。
