The effects of acute renal failure on drug metabolism

Expert Opin Drug Metab Toxicol. 2014 Jan;10(1):11-23. doi: 10.1517/17425255.2013.835802. Epub 2013 Sep 28.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / pathology*
  • Animals
  • Critical Illness
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Disease Models, Animal
  • Humans
  • Inactivation, Metabolic
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Pharmaceutical Preparations / administration & dosage
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / pathology

Substances

  • Pharmaceutical Preparations
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A