Optimising the use of medicines to reduce acute kidney injury in children and babies

• Published in: Pharmacology & therapeutics (Oxford) Vol. 174; pp. 55 - 62
• Main Authors: Oni, L, Hawcutt, D B, Turner, M A, Beresford, M W, McWilliam, S, Barton, C, Park, B K, Murray, P, Wilm, B, Copple, I, Floyd, R, Peak, M, Sharma, A, Antoine, D J
• Format: Journal Article
• Language: English
• Published: England 01-06-2017
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - genetics; Acute Kidney Injury - prevention & control; Adolescent; Age Factors; Anti-Bacterial Agents - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Antineoplastic Agents - adverse effects; Biomarkers - urine; Child; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - prevention & control; Humans; Infant; Off-Label Use; Pharmacogenetics; Nephrotoxic; Acute kidney injury; Children
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2017.02.018

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.