Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion

Toxins (Basel). 2020 Jun 12;12(6):391. doi: 10.3390/toxins12060391.


In chronic kidney disease (CKD), the secretion of uremic toxins is compromised leading to their accumulation in blood, which contributes to uremic complications, in particular cardiovascular disease. Organic anion transporters (OATs) are involved in the tubular secretion of protein-bound uremic toxins (PBUTs). However, OATs also handle a wide range of drugs, including those used for treatment of cardiovascular complications and their interaction with PBUTs is unknown. The aim of this study was to investigate the interaction between commonly prescribed drugs in CKD and endogenous PBUTs with respect to OAT1-mediated uptake. We exposed a unique conditionally immortalized proximal tubule cell line (ciPTEC) equipped with OAT1 to a panel of selected drugs, including angiotensin-converting enzyme inhibitors (ACEIs: captopril, enalaprilate, lisinopril), angiotensin receptor blockers (ARBs: losartan and valsartan), furosemide and statins (pravastatin and simvastatin), and evaluated the drug-interactions using an OAT1-mediated fluorescein assay. We show that selected ARBs and furosemide significantly reduced fluorescein uptake, with the highest potency for ARBs. This was exaggerated in presence of some PBUTs. Selected ACEIs and statins had either no or a slight effect at supratherapeutic concentrations on OAT1-mediated fluorescein uptake. In conclusion, we demonstrate that PBUTs may compete with co-administrated drugs commonly used in CKD management for renal OAT1 mediated secretion, thus potentially compromising the residual renal function.

Keywords: OAT1-mediated transport; chronic kidney disease management; drug-toxin interaction; protein-bound uremic toxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Cell Line
  • Furosemide / pharmacology
  • Humans
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Kidney Tubules / physiopathology
  • Organic Anion Transport Protein 1 / metabolism*
  • Prescription Drugs / metabolism
  • Prescription Drugs / pharmacology*
  • Renal Elimination / drug effects*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Sodium Potassium Chloride Symporter Inhibitors / pharmacology
  • Toxins, Biological / blood*
  • Uremia / blood
  • Uremia / drug therapy*
  • Uremia / physiopathology


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Organic Anion Transport Protein 1
  • Prescription Drugs
  • SLC22A6 protein, human
  • Sodium Potassium Chloride Symporter Inhibitors
  • Toxins, Biological
  • Furosemide