Protein-bound uremic solutes: the forgotten toxins

Kidney Int Suppl. 2001 Feb;78:S266-70. doi: 10.1046/j.1523-1755.2001.59780266.x.


The present concept of dialysis focuses mainly on the removal of small water-soluble compounds, and also, the currently applied kinetic parameters of dialysis adequacy are based on the behavior of water-soluble compounds. Nevertheless, many of the currently known biological effects in uremia are attributable to compounds with different physicochemical characteristics, and among these, protein-bound solutes play an important role. In this article, we review the characteristics and consequences of changes in protein binding in uremia, as well as the toxicity of the protein-bound uremic solutes 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indoxyl sulfate, hippuric acid, homocysteine, and p-cresol. Starting from the example of p-cresol, we then summarize the impact of protein-binding on dialytic removal, whereby it is concluded that this removal is largely hampered by this protein-binding compared with that of classic markers such as urea and creatinine. Alternative removal strategies, such as strategies to modify intestinal generation or absorption, are considered.

Publication types

  • Review

MeSH terms

  • Animals
  • Cresols / metabolism
  • Furans / metabolism
  • Hippurates / metabolism
  • Homocysteine / metabolism
  • Humans
  • Indican / metabolism
  • Intestinal Mucosa / metabolism
  • Kinetics
  • Propionates / metabolism
  • Protein Binding
  • Proteins / metabolism*
  • Renal Dialysis
  • Toxins, Biological / metabolism*
  • Uremia / metabolism*
  • Uremia / therapy


  • Cresols
  • Furans
  • Hippurates
  • Propionates
  • Proteins
  • Toxins, Biological
  • Homocysteine
  • 4-cresol
  • 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid
  • Indican
  • hippuric acid