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Transporter-Mediated Interactions Between Uremic Toxins and Drugs: A Hidden Driver of Toxicity in Chronic Kidney

Pierre Spicher1,2, François Brazier1,3, Solène M Laville1,4

  • 1MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France.

International Journal of Molecular Sciences
|July 12, 2025
PubMed

Insights

Chronic kidney disease (CKD) involves uremic toxin buildup, like indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Transporter mechanisms influence their elimination and potential drug interactions, impacting patient management.

Area of Science:

  • Nephrology
  • Pharmacology
  • Toxicology

Background:

  • Chronic kidney disease (CKD) leads to uremic toxin (UT) accumulation due to poor kidney function.
  • Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are key UTs, difficult to remove by dialysis due to high protein binding.

Purpose of the Study:

  • To review transporter-mediated mechanisms governing the disposition of IS, PCS, and their precursors (indole, p-cresol).
  • To examine potential interactions between these UTs and commonly prescribed CKD drugs sharing transporter pathways.
  • To highlight the clinical implications of these drug-toxin interactions in CKD management.

Main Methods:

  • Literature review focusing on transporter roles in UT disposition.
  • Analysis of UT interactions with drug substrates/inhibitors of shared transporters.
  • Examination of physiological barriers: intestinal, blood-brain, and renal proximal tubule.

Main Results:

  • Transporter proteins significantly influence the distribution and elimination of IS, PCS, indole, and p-cresol across critical barriers.
  • Drug-toxin interactions involving shared transporters can alter UT pharmacokinetics and toxicity.
  • These interactions are poorly understood and often overlooked in clinical practice.

Conclusions:

  • Understanding transporter-mediated UT disposition is crucial for managing CKD patients.
  • Identifying drug-toxin interactions can optimize pharmacotherapy and improve patient outcomes.
  • Further research is needed to characterize these interactions for better clinical decision-making in polypharmacy settings.
Keywords:
blood–brain barrierchronic kidney diseaseindoleindoxyl sulfateintestinal barrierorganic anion transporterp-cresolpara-cresyl sulfaterenal barriersolute carrier transporter

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