Identification and Quantitative Assessment of Uremic Solutes as Inhibitors of Renal Organic Anion Transporters, OAT1 and OAT3

Mol Pharm. 2016 Sep 6;13(9):3130-40. doi: 10.1021/acs.molpharmaceut.6b00332. Epub 2016 Aug 9.


One of the characteristics of chronic kidney disease (CKD) is the accumulation of uremic solutes in the plasma. Less is known about the effects of uremic solutes on transporters that may play critical roles in pharmacokinetics. We evaluated the effect of 72 uremic solutes on organic anion transporter 1 and 3 (OAT1 and OAT3) using a fluorescent probe substrate, 6-carboxyfluorescein. A total of 12 and 13 solutes were identified as inhibitors of OAT1 and OAT3, respectively. Several of them inhibited OAT1 or OAT3 at clinically relevant concentrations and reduced the transport of other OAT1/3 substrates in vitro. Review of clinical studies showed that the active secretion of most drugs that are known substrates of OAT1/3 deteriorated faster than the renal filtration in CKD. Collectively, these data suggest that through inhibition of OAT1 and OAT3, uremic solutes contribute to the decline in renal drug clearance in patients with CKD.

Keywords: chronic kidney disease; organic anion transporter; regulatory science; uremic solute.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Fluoresceins / metabolism
  • Humans
  • Models, Biological
  • Organic Anion Transport Protein 1 / analysis
  • Organic Anion Transport Protein 1 / metabolism*
  • Organic Anion Transporters, Sodium-Independent / analysis
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Renal Insufficiency, Chronic / metabolism*


  • Fluoresceins
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters, Sodium-Independent
  • organic anion transport protein 3
  • 6-carboxyfluorescein