Protein-bound molecules: a large family with a bad character.
Many small solutes excreted by the kidney are bound to plasma proteins, chiefly albumin, in the circulation. The combination of protein binding and tubular secretion allows the kidney to reduce the free, unbound concentrations of such solutes to lower levels than could be obtained by tubular secretion alone. Protein-bound solutes accumulate in the plasma when the kidneys fail, and the free, unbound levels of these solutes increase more than their total plasma levels owing to competition for binding sites on plasma proteins. Given the efficiency by which the kidney can clear protein-bound solutes, it is tempting to speculate that some compounds in this class are important uremic toxins. Studies to date have focused largely on two specific protein-bound solutes: indoxyl sulfate and p-cresyl sulfate. The largest body of evidence suggests that both of these compounds contribute to cardiovascular disease, and that indoxyl sulfate contributes to the progression of chronic kidney disease. Other protein-bound solutes have been investigated to a much lesser extent, and could in the future prove to be even more important uremic toxins.
Department of Medicine, VA Palo Alto Healthcare System and Stanford University, Palo Alto, CA.
Tammy L
TL
Sirich
Department of Medicine, VA Palo Alto Healthcare System and Stanford University, Palo Alto, CA. Electronic address: twmeyer@stanford.edu.
Timothy W
TW
Meyer
Aix-Marseille University, INSERM UMR_S 1076, Marseille, France; Centre de Nephrologie et Transplantation Renale, Assistance-Publique Hopitaux de Marseille, Marseille, France.
Bertrand
B
Gondouin
Aix-Marseille University, INSERM UMR_S 1076, Marseille, France; Centre de Nephrologie et Transplantation Renale, Assistance-Publique Hopitaux de Marseille, Marseille, France.
Philippe
P
Brunet
Department of Advanced Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toshimitsu
T
Niwa
D002318:Cardiovascular Diseases / Q000209:etiology; D003072:Cognition Disorders / Q000209:etiology; D003408:Cresols / Q000378:metabolism*; D006801:Humans; D007200:Indican / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology; D011485:Protein Binding; D013463:Sulfuric Acid Esters / Q000378:metabolism*
D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican
Uremia; protein-bound; renal dialysis