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著者: Raymond Vanholder, Rita De Smet, Griet Glorieux, Angel Argilés, Ulrich Baurmeister, Philippe Brunet, William Clark, Gerald Cohen, Peter Paul De Deyn, Reinhold Deppisch, Beatrice Descamps-Latscha, Thomas Henle, Achim Jörres, Horst Dieter Lemke, Ziad A Massy, Jutta Passlick-Deetjen, Mariano Rodriguez, Bernd Stegmayr, Peter Stenvinkel, Ciro Tetta, Christoph Wanner, Walter Zidek, European Uremic Toxin Work Group (EUTox)
雑誌名: Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x.
Abstract/Text
BACKGROUND: The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications.
METHODS: An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002.
RESULTS: For all compounds, CU and/or CMAX exceeded CN. Molecular weight was lower than 500 D for 68 compounds; of the remaining 22 middle molecules, 12 exceeded 12,000 D. CU ranged from 32.0 ng/L (methionine-enkephalin) up to 2.3 g/L (urea). CU in the ng/L range was found especially for the middle molecules (10/22; 45.5%), compared with 2/68 (2.9%) for a molecular weight <500 D (P < 0.002). Twenty-five solutes (27.8%) were protein bound. Most of them had a molecular weight <500 D except for leptin and retinol-binding protein. The ratio CU/CN, an index of the concentration range over which toxicity is exerted, exceeded 15 in the case of 20 compounds. The highest values were registered for several guanidines, protein-bound compounds, and middle molecules, to a large extent compounds with known toxicity. A ratio of CMAX/CU <4, pointing to a Gaussian distribution, was found for the majority of the compounds (74/90; 82%). For some compounds, however, this ratio largely exceeded 4 [e.g., for leptin (6.81) or indole-3-acetic acid (10.37)], pointing to other influencing factors than renal function, such as gender, genetic predisposition, proteolytic breakdown, posttranslation modification, general condition, or nutritional status.
CONCLUSION: Concentrations of retention solutes in uremia vary over a broad range, from nanograms per liter to grams per liter. Low concentrations are found especially for the middle molecules. A substantial number of molecules are protein bound and/or middle molecules, and many of these exert toxicity and are characterized by a high range of toxic over normal concentration (CU/CN ratio). Hence, uremic retention is a complex problem that concerns many more solutes than the current markers of urea and creatinine alone. This list provides a basis for systematic analytic approaches to map the relative importance of the enlisted families of toxins.
PMID 12675874 Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x.
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