title: Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.
abstract: Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth.
authors: General Intensive Care Unit, St. George's Hospital, London SW17 0QT, UK. johndixon3@nhs.net.
authors: John
authors: J
authors: Dixon
authors: General Intensive Care Unit, St. George's Hospital, London SW17 0QT, UK. klane@sgul.ac.uk.
authors: Katie
authors: K
authors: Lane
authors: Division of Clinical Sciences, St. George's, University of London, London SW17 0RE, UK. imacphee@sgul.ac.uk.
authors: Iain
authors: I
authors: Macphee
authors: General Intensive Care Unit, St. George's Hospital, London SW17 0QT, UK. bphilips@sgul.ac.uk.
authors: Barbara
authors: B
authors: Philips
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology; D027321:Anion Transport Proteins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System