Protein-bound uremic solutes: the forgotten toxins.
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.
Vanholder
R
R
Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium. raymond.vanholder@rug.ac.be
De Smet
R
R
Lameire
N
N
D000818:Animals; D003408:Cresols / Q000378:metabolism; D005663:Furans / Q000378:metabolism; D006626:Hippurates / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007200:Indican / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D011422:Propionates / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D006435:Renal Dialysis; D014118:Toxins, Biological / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism* / Q000628:therapy
D003408:Cresols; D005663:Furans; D006626:Hippurates; D011422:Propionates; D011506:Proteins; D014118:Toxins, Biological; D006710:Homocysteine; C032538:4-cresol; C041693:3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; D007200:Indican; C030514:hippuric acid