The effects of acute renal failure on drug metabolism.
BACKGROUND
Acute kidney injury (AKI) is common in all hospital admissions and affects 10% of acute admissions in hospital. It increases the risk of adverse events and mortality, although the precise reasons for this are still unclear. The impact of chronic kidney disease (CKD) on nonrenal drug clearance is increasingly apparent and is now considered an important factor by the Food and Drug Administration for drug dose recommendations in CKD.


METHODS
This review explores the evidence of the impact of AKI on nonrenal drug metabolism. The review uses evidence from investigations of both CKD and AKI describing the manner of the inhibition and the most likely mediators of renohepatic crosstalk. The review also considers other forms of nonrenal clearance, including gut metabolism. Changes are related to critical illness in general, where appropriate.


CONCLUSIONS
Renal and hepatic interactions are highly complex with increasing evidence for an important relationship between AKI and hepatic metabolism. Current recommended dosing regimens are inadequate for AKI patients and much greater understanding of the interaction between the kidney and liver is required. More extensive therapeutic drug monitoring may be required to optimize drug regimens.
St George's, University of London, Division of Clinical Sciences , Cranmer Terrace, London SW17 0RE , UK +0044 208 725 5071 ; bphilips@sgul.ac.uk.
Barbara J
BJ
Philips
Katie
K
Lane
John
J
Dixon
Iain
I
Macphee
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D016638:Critical Illness; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008658:Inactivation, Metabolic; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy / Q000473:pathology
D004364:Pharmaceutical Preparations; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A