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Uremic Toxins and their Relation to Dialysis Efficacy.
Blood Purif. 2019; 48(4):299-314.BP

Abstract

Toxin retention is felt to be a major contributor to the development of uremia in patients with advanced chronic kidney disease and end-stage renal disease (ESRD). Uremic retention compounds are classically divided into 3 categories: small solutes, middle molecules, and protein-bound toxins. Compounds comprising the first category, for which the upper molecular weight limit is generally considered to be 500 Da, possess a high degree of water solubility and minimal or absent protein binding. The second category of middle molecules has largely evolved now to be synonymous with peptides and proteins that accumulate in uremia. Although not precisely defined, low-molecular weight proteins as a class have a molecular weight spectrum ranging from approximately 500 to 60,000 daltons. The final category of uremic retention compounds is protein-bound uremic toxins (PBUTs). As opposed to the above small, highly water-soluble toxins, which are largely by-products of protein metabolism, PBUTs have diverse origins and possess chemical characteristics that preclude the possibility of circulation in an unbound form despite being of low molecular weight. This review is the first in a series of papers designed to provide the current state of the art for extracorporeal treatment of ESRD. Subsequent papers in this series will address membranes, mass transfer mechanisms, and future directions. For small solutes and middle molecules, particular emphasis is placed on the important clinical trials that comprise the evidence base regarding the influence of dialytic solute removal on outcome. Because such trials do not exist for PBUTs, the discussion here is instead focused on solute characteristics and renal elimination mechanisms.

Authors+Show Affiliations

Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana, USA, clarkw@purdue.edu.Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana, USA.Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana, USA.International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy. Department of Medicine, Università degli Studi di Padova, Padova, Italy.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31563911

Citation

Clark, William R., et al. "Uremic Toxins and Their Relation to Dialysis Efficacy." Blood Purification, vol. 48, no. 4, 2019, pp. 299-314.
Clark WR, Dehghani NL, Narsimhan V, et al. Uremic Toxins and their Relation to Dialysis Efficacy. Blood Purif. 2019;48(4):299-314.
Clark, W. R., Dehghani, N. L., Narsimhan, V., & Ronco, C. (2019). Uremic Toxins and their Relation to Dialysis Efficacy. Blood Purification, 48(4), 299-314. https://doi.org/10.1159/000502331
Clark WR, et al. Uremic Toxins and Their Relation to Dialysis Efficacy. Blood Purif. 2019;48(4):299-314. PubMed PMID: 31563911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uremic Toxins and their Relation to Dialysis Efficacy. AU - Clark,William R, AU - Dehghani,Nader Laal, AU - Narsimhan,Vivek, AU - Ronco,Claudio, Y1 - 2019/09/27/ PY - 2019/04/07/received PY - 2019/07/21/accepted PY - 2019/9/30/pubmed PY - 2020/5/16/medline PY - 2019/9/30/entrez KW - Middle molecule KW - Protein binding KW - Small solute KW - Toxin KW - Urea KW - Uremia KW - β2-Microglobulin SP - 299 EP - 314 JF - Blood purification JO - Blood Purif VL - 48 IS - 4 N2 - Toxin retention is felt to be a major contributor to the development of uremia in patients with advanced chronic kidney disease and end-stage renal disease (ESRD). Uremic retention compounds are classically divided into 3 categories: small solutes, middle molecules, and protein-bound toxins. Compounds comprising the first category, for which the upper molecular weight limit is generally considered to be 500 Da, possess a high degree of water solubility and minimal or absent protein binding. The second category of middle molecules has largely evolved now to be synonymous with peptides and proteins that accumulate in uremia. Although not precisely defined, low-molecular weight proteins as a class have a molecular weight spectrum ranging from approximately 500 to 60,000 daltons. The final category of uremic retention compounds is protein-bound uremic toxins (PBUTs). As opposed to the above small, highly water-soluble toxins, which are largely by-products of protein metabolism, PBUTs have diverse origins and possess chemical characteristics that preclude the possibility of circulation in an unbound form despite being of low molecular weight. This review is the first in a series of papers designed to provide the current state of the art for extracorporeal treatment of ESRD. Subsequent papers in this series will address membranes, mass transfer mechanisms, and future directions. For small solutes and middle molecules, particular emphasis is placed on the important clinical trials that comprise the evidence base regarding the influence of dialytic solute removal on outcome. Because such trials do not exist for PBUTs, the discussion here is instead focused on solute characteristics and renal elimination mechanisms. SN - 1421-9735 UR - https://www.unboundmedicine.com/medline/citation/31563911/Uremic_Toxins_and_their_Relation_to_Dialysis_Efficacy_ DB - PRIME DP - Unbound Medicine ER -