title: Optimising the use of medicines to reduce acute kidney injury in children and babies.
abstract: The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs. This may be related to physiological (differential expressions of cytochrome P450 enzymes or variable glomerular filtration rates at different ages for example) and psychological (increasing autonomy and risk perception in teenage years) changes. Increasing numbers of children are surviving life-threatening childhood conditions due to medical advances. This means there is an increasing population who are at risk of the consequences of the long-term, early exposure to nephrotoxic agents. The kidney is an organ that is particularly vulnerable to damage as a consequence of drugs. Drug-induced acute kidney injury (AKI) episodes in children and babies are principally due to non-steroidal anti-inflammatory drugs, antibiotics or chemotherapeutic agents. The renal tubules are vulnerable to injury because of their concentrating ability and high-energy hypoxic environment. This review focuses on drug-induced AKI and the methods to minimise its effect, including general management plus the role of child-specific pharmacokinetic data, the use of pharmacogenomics and early detection of AKI using urinary biomarkers and electronic triggers.
authors.affiliation: Department of Women's & Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Nephrology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK. Electronic address: louise.oni@liverpool.ac.uk.
authors.forename: L
authors.initials: L
authors.lastname: Oni
authors.affiliation: Department of Women's & Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Pharmacology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Hawcutt
authors.affiliation: Department of Women's & Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Centre for Better Births, Liverpool Women's Hospital, Liverpool, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: Department of Women's & Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Beresford
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: S
authors.initials: S
authors.lastname: McWilliam
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Oncology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
authors.forename: C
authors.initials: C
authors.lastname: Barton
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: B K
authors.initials: BK
authors.lastname: Park
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: P
authors.initials: P
authors.lastname: Murray
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: B
authors.initials: B
authors.lastname: Wilm
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: I
authors.initials: I
authors.lastname: Copple
authors.affiliation: Department of Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Floyd
authors.affiliation: Department of Research and Development, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
authors.forename: M
authors.initials: M
authors.lastname: Peak
authors.affiliation: Department of Nephrology, The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Antoine
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D000293:Adolescent; D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000652:urine; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D056687:Off-Label Use; D010597:Pharmacogenetics
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D015415:Biomarkers
keywords: Acute kidney injury; Children; Nephrotoxic