The effects of acute renal failure on drug metabolism

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.

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.

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.