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Effects of chronic renal failure on liver drug transporters

Judith Naud1, Josée Michaud, Francois A Leblond

  • 1Service de Néphrologie et Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Université de Montréal, Québec, Canada.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|October 18, 2007
PubMed

Insights

Chronic renal failure (CRF) decreases liver drug uptake transporters like organic anion transporting polypeptide 2 and increases drug extrusion transporters such as P-glycoprotein and multidrug resistance protein 2. Uremic toxins likely cause these changes.

Area of Science:

  • Pharmacology
  • Nephrology
  • Hepatology

Background:

  • Chronic renal failure (CRF) impairs liver drug metabolism and intestinal drug transporters.
  • Limited research exists on CRF's impact on hepatic drug transporters.

Purpose of the Study:

  • To investigate the effects of CRF on key liver drug transporters involved in uptake (Oatp2) and extrusion (P-gp, MRP2).

Main Methods:

  • Compared control and CRF rats, assessing transporter protein and mRNA levels.
  • Evaluated transporter activity and the impact of CRF serum on cultured hepatocytes.

Main Results:

  • CRF rats showed reduced creatinine clearance, increased P-gp expression/mRNA, and increased MRP2 mRNA.
  • Oatp2 protein expression was decreased in CRF rats, while its mRNA remained unchanged.
  • Uremic serum mimicked these transporter alterations in hepatocytes.

Conclusions:

  • CRF alters liver drug transporters, decreasing uptake (Oatp2) and increasing extrusion (P-gp, MRP2).
  • Uremic mediators are implicated in causing these transporter modifications.

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