Garnier Anne-Sophie, Dellamaggiore Juliette, Brilland Benoit, Lagarce Laurence, Abgueguen Pierre, Furber Alain, Legrand Erick, Subra Jean-François, Drablier Guillaume, Augusto Jean-François
Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, 49000 Angers, France.
Faculté de Pharmacie, Université d'Angers, 49000 Angers, France.
J Clin Med. 2020 Jun 27;9(7):2022. doi: 10.3390/jcm9072022.
Amoxicillin (AMX)-induced crystal nephropathy (AICN) is considered as a rare complication of high dose intravenous (IV) AMX administration. However, recently, its incidence seems to be increasing based on French pharmacovigilance centers. Occurrence of AICN has been observed mainly with IV administration of AMX and mostly under doses over 8 g/day. Given that pharmacovigilance data are based on declaration, the real incidence of AICN may be underestimated. Thus, the primary objective of the present study was to determine the incidence of AICN in the current practice.
We conducted a retrospective study between 1 January 2015 and 31 December 2017 in Angers University Hospital. Inclusion criteria were age over 18 years-old and IV AMX administration of at least 8 g/day for more than 24 h. Patients admitted directly into the intensive care units were excluded. Medical records of patients that developed Kidney Disease:Improving Global Outcome (KDIGO) stage 2-3 acute kidney injury (AKI) were reviewed by a nephrologist and a specialist in pharmacovigilance. AICN was retained if temporality analysis was conclusive, after exclusion of other causes of AKI, in absence of other nephrotoxic drug administration.
A total of 1303 patients received IV AMX for at least 24 h. Among them, 358 (27.5%) were exposed to AMX doses of at least 8 g/day and were included. Patients were predominantly males (68.2%) with a mean age of 69.1 years-old. AMX was administered for a medical reason in 78.5% of cases. Patients received a median dose of AMX of 12 g/day (152.0 mg/kg/day). Seventy-three patients (20.4%) developed AKI, 42 (56.8%) of which were KDIGO stage 2 or 3. Among the latter, AICN diagnosis was retained in 16 (38.1%) patients, representing an incidence of 4.47% of total patients exposed to high IV AMX doses. Only female gender was associated with an increased risk of AICN. AMX dose was not significantly associated with AICN development.
This study suggests a high incidence of AICN in patients receiving high IV AMX doses, representing one third of AKI causes in our study. Female gender appeared as the sole risk factor for AICN in this study.
阿莫西林（AMX）诱导的结晶性肾病（AICN）被认为是高剂量静脉注射（IV）AMX治疗的一种罕见并发症。然而，最近根据法国药物警戒中心的数据，其发病率似乎在上升。AICN主要在静脉注射AMX时出现，且大多发生在每日剂量超过8克的情况下。鉴于药物警戒数据基于申报情况，AICN的实际发病率可能被低估。因此，本研究的主要目的是确定当前临床实践中AICN的发病率。
我们于2015年1月1日至2017年12月31日在昂热大学医院进行了一项回顾性研究。纳入标准为年龄超过18岁且静脉注射AMX至少8克/天持续超过24小时。直接入住重症监护病房的患者被排除。由一名肾病学家和一名药物警戒专家对出现肾脏病：改善全球预后（KDIGO）2 - 3期急性肾损伤（AKI）的患者病历进行审查。在排除其他AKI病因且未使用其他肾毒性药物的情况下，如果时间顺序分析具有决定性，则认定为AICN。
共有1303例患者接受静脉注射AMX至少24小时。其中，358例（27.5%）接受了至少8克/天的AMX剂量并被纳入研究。患者以男性为主（68.2%），平均年龄为69.1岁。78.5%的病例使用AMX是出于医疗原因。患者接受AMX的中位剂量为12克/天（152.0毫克/千克/天）。73例患者（20.4%）发生了AKI，其中42例（56.8%）为KDIGO 2期或3期。在后者中，16例（38.1%）患者被诊断为AICN，占接受高剂量静脉注射AMX患者总数的4.47%。仅女性性别与AICN风险增加相关。AMX剂量与AICN的发生无显著相关性。
本研究表明接受高剂量静脉注射AMX的患者中AICN发病率较高，在我们的研究中占AKI病因的三分之一。在本研究中，女性性别是AICN的唯一风险因素。
