title: Protein-bound toxins: has the Cinderella of uraemic toxins turned into a princess?
abstract: Chronic kidney disease (CKD) has emerged as a global public health problem. Although the incidence and prevalence of CKD vary from one country to another, the estimated worldwide prevalence is 8-16%. The complications associated with CKD include progression to end-stage renal disease (ESRD), mineral and bone disorders, anaemia, cognitive decline and elevated all-cause and cardiovascular (CV) mortality. As a result of progressive nephron loss, patients with late-stage CKD are permanently exposed to uraemic toxins. These toxins have been classified into three groups as a function of the molecular mass: small water-soluble molecules, middle molecules and protein-bound uraemic toxins. The compounds can also be classified according to their origin (i.e. microbial or not) or their protein-binding ability. The present review will focus on the best-characterized protein-bound uraemic toxins, namely indoxylsulfate (IS), indole acetic acid (IAA) and p-cresylsulfate (PCS, a cresol metabolite). Recent research suggests that these toxins accelerate the progression of CV disease, kidney disease, bone disorders and neurological complications. Lastly, we review therapeutic approaches that can be used to decrease toxin levels.
authors: INSERM U1088, Jules Verne University of Picardy, Amiens 80000, France.|Clinical Research Centre Division of Clinical Pharmacology, Amiens University Hospital, Amiens 80000, France.
authors: Sophie
authors: S
authors: Liabeuf
authors: Nephrology Unit, Ambroise Paré Hospital, AP-HP, Université de Versailles Saint-Quentin en Yvelines, Boulogne-Billancourt F-92100, France.|INSERM U1018, Université de Versailles Saint-Quentin en Yvelines, Université Paris-Saclay, Villejuif 94804, France.
authors: Cédric
authors: C
authors: Villain
authors: Nephrology Unit, Ambroise Paré Hospital, AP-HP, Université de Versailles Saint-Quentin en Yvelines, Boulogne-Billancourt F-92100, France ziad.massy@aphp.fr.|INSERM U1018, Université de Versailles Saint-Quentin en Yvelines, Université Paris-Saclay, Villejuif 94804, France.
authors: Ziad A
authors: ZA
authors: Massy
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology*; D003408:Cresols / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007200:Indican / Q000378:metabolism / Q000633:toxicity*; D007210:Indoleacetic Acids / Q000378:metabolism / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000378:metabolism / Q000633:toxicity*; D014511:Uremia / Q000150:complications* / Q000378:metabolism
chemical_list: D003408:Cresols; D007210:Indoleacetic Acids; D011506:Proteins; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; C030737:indoleacetic acid; D007200:Indican
keywords: nephrology; toxins; uraemic