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Open AccessArticle

High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin

Service de Néphrologie-Dialyse-Transplantation, Université d’Angers, CHU Angers, 49000 Angers, France
Faculté de Pharmacie, Université d’Angers, 49000 Angers, France
Service de Pharmacologie-Toxicologie et Pharmacovigilance, Université d’Angers, CHU d’Angers, 49000 Angers, France
Service de Maladies Infectieuses et Tropicales, Université d’Angers, CHU d’Angers, 49000 Angers, France
UMR CNRS 6015–INSERM U1083, Équipe Physiopathologie Cardiovasculaire, UFR Santé, 49000 Angers, France
Service de Rhumatologie, Université d’Angers, CHU d’Angers, 49000 Angers, France
CRCINA, INSERM, Université de Nantes, 49000 Angers, France
Université d’Angers, 49000 Angers, France
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2022;
Received: 31 May 2020 / Revised: 24 June 2020 / Accepted: 24 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue Prevention and Treatment of Acute Kidney Injury)
Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. View Full-Text
Keywords: amoxicillin; crystalluria; acute kidney injury; incidence amoxicillin; crystalluria; acute kidney injury; incidence
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Garnier, A.-S.; Dellamaggiore, J.; Brilland, B.; Lagarce, L.; Abgueguen, P.; Furber, A.; Legrand, E.; Subra, J.-F.; Drablier, G.; Augusto, J.-F. High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin. J. Clin. Med. 2020, 9, 2022.

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