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Biochemical and clinical impact of organic uremic retention solutes : a comprehensive update

Raymond Vanholder (UGent) , Anneleen Pletinck (UGent) , Eva Schepers (UGent) and Griet Glorieux (UGent)
(2018) TOXINS. 10(1).
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Abstract
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [(2)-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.
Keywords
CHRONIC KIDNEY-DISEASE, CHRONIC-RENAL-FAILURE, GLYCATION END-PRODUCTS, RETINOL-BINDING-PROTEIN, COLONY-STIMULATING FACTOR, ATRIAL-NATRIURETIC-PEPTIDE, CORONARY-ARTERY-DISEASE, FURAN, DICARBOXYLIC-ACID, TOXIN PHENYLACETIC ACID, NITRIC-OXIDE SYNTHASE, uremic toxins, uremic toxicity, uremia, Chronic Kidney Disease, CKD, cardiovascular disease, inflammation, fibrosis, patho-physiology CKD, middle molecules, protein bound uremic solutes, water-soluble uremic, solutes

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Chicago
Vanholder, Raymond, Anneleen Pletinck, Eva Schepers, and Griet Glorieux. 2018. “Biochemical and Clinical Impact of Organic Uremic Retention Solutes : a Comprehensive Update.” Toxins 10 (1).
APA
Vanholder, R., Pletinck, A., Schepers, E., & Glorieux, G. (2018). Biochemical and clinical impact of organic uremic retention solutes : a comprehensive update. TOXINS, 10(1).
Vancouver
1.
Vanholder R, Pletinck A, Schepers E, Glorieux G. Biochemical and clinical impact of organic uremic retention solutes : a comprehensive update. TOXINS. 2018;10(1).
MLA
Vanholder, Raymond, Anneleen Pletinck, Eva Schepers, et al. “Biochemical and Clinical Impact of Organic Uremic Retention Solutes : a Comprehensive Update.” TOXINS 10.1 (2018): n. pag. Print.
@article{8569371,
  abstract     = {In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [(2)-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.},
  articleno    = {33},
  author       = {Vanholder, Raymond and Pletinck, Anneleen and Schepers, Eva and Glorieux, Griet},
  issn         = {2072-6651},
  journal      = {TOXINS},
  keywords     = {CHRONIC KIDNEY-DISEASE,CHRONIC-RENAL-FAILURE,GLYCATION END-PRODUCTS,RETINOL-BINDING-PROTEIN,COLONY-STIMULATING FACTOR,ATRIAL-NATRIURETIC-PEPTIDE,CORONARY-ARTERY-DISEASE,FURAN,DICARBOXYLIC-ACID,TOXIN PHENYLACETIC ACID,NITRIC-OXIDE SYNTHASE,uremic toxins,uremic toxicity,uremia,Chronic Kidney Disease,CKD,cardiovascular disease,inflammation,fibrosis,patho-physiology CKD,middle molecules,protein bound uremic solutes,water-soluble uremic,solutes},
  language     = {eng},
  number       = {1},
  pages        = {57},
  title        = {Biochemical and clinical impact of organic uremic retention solutes : a comprehensive update},
  url          = {http://dx.doi.org/10.3390/toxins10010033},
  volume       = {10},
  year         = {2018},
}

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