Table of contents
- Introduction to the EUTox database
- Data stored in the database
- The website interface
- Analytical assessment
- Submitting new research data
- Publication and re-use
Introduction to the EUTox database
The European Uremic Solutes Database (EUTox-DB) is an initiative of the European Work Group on Uremic toxins (EUTox) of the European Society for Artificial Organs (ESAO). The purpose of the Database is to systematically capture and assess uremic toxins and solutes that accumulate in the plasma during the later stages of chronic kidney disease. The uremic plasmatic concentrations and the known pathologic implications are extracted from the scientific literature. The Database has been designed as an interactive tool that both provides and collects information on biological significance of uremic solutes using an easy-to-use web interface.
The starting point of the Database was a review article in Kidney International on uremic compounds published in 2003 by Prof. Raymond Vanholder, founder of the the EUTox Work Group (1), and further by Meert et al (2) and Duranton et al (3), which provided additional data and new insights into the complexity of uremic toxins.
Based on these results, a system was developed to characterise and include new research data into the Database using a peer-review based approach. All information presented on this website is based on publication available in Pubmed. For each result, a direct link to the respective entry in Pubmed is provided for further study.
Caution: The EUTox Work Group is unable to judge the validity of measured plasmatic concentrations when adding it to the Database. We trust the researcher using the Database to double-check the original data. The Database being an interactive tool, its results may change over time. For this reason, we also advise users to save results locally.
Data stored in the database
The purpose of the Database is to register and characterise compounds known to display increased plasmatic concentrations during the last stage of chronic kidney disease. For this, the name and description of the compound as well as plasmatic levels from healthy controls and uremic patients are stored. This is the minimum needed information to include a compound in the Database.
Additional results (plasma concentrations) from healthy controls and uremic patients can be added to an existing compound. There is no limit on the number of reported concentrations. Each result should include: the population mean in mass concentration (i.e. mg/L) and standard deviation, the number of samples used to determine the mean, as well as the Pubmed reference.
Finally, pathological associations of solutes are displayed. To be included, pathological associations linked to a given compound should rely on in vivo evidence, not necessarily in the context of uraemia. Pathological associations are classified by biological systems, based on a publication from Prof. Angel Argilés, chairman of the EUTox group from 2011-2018 (4):
- Central nervous system
- Peripheral nervous system
- Skin Endocrinology
- Nutrition Immunity
The website interface
The SOLUTE LIST shows all uremic solutes currently recorded in the Database with a summary of respective results. The list is sortable by clicking on the title of a table header. Clicking on the compounds name leads to the respective SOLUTE DETAILS page.
The SOLUTE DETAILS show all information recorded for a single compound. Notably, it details the base data, published healthy and uremic concentrations and respective Pubmed references on which the statistical analysis is performed. It is possible to switch to a different solute using the dropdown list provided at the top of the page.
The STATISTICS page shows a selection of statistical calculations performed on the entire list of compounds as a whole, such as the total number of recorded compounds, their distributions based on their physicochemical classification and on the groups of pathological associations. These calculations will be further enhanced in the future - the EUTox group welcomes suggestions on what questions would be of interest.
The LOGIN page allows registered users to log-in and add new data to the Database. To register and submit data to the, please use the form under REGISTER.
The EUTox Work Group is unable to judge the validity of all measured plasmatic concentrations added to the Database. However, we provide two methods to assess whether the entire collection of healthy or uremic concentrations are within acceptable boundaries or if one or more reported concentrations appear to be out of those boundaries. One analysis is purely statistical, based on analysis of variance (ANOVA) and the other based on the reported highest and lowest concentrations in the literature developed by Meert et al (2).
Method using ANOVA
To perform an ANOVA test, the following criteria have to be met for each concentration in question:
ANOVA will first calculate a mean from the mean of each concentration ("Grand mean"). This grand mean is displayed on the SOLUTE LIST and in SOLUTE DETAILS. Next, the ANOVA test verifies each concentration for a significant difference to the grand mean. The website indicates the result of the ANOVA test with the following color codes:
- An arithmetic mean
- A standard deviation
- A total sample count of at least 2
- Black: ANOVA was not possible because one or more criteria were not met.
- Blue: ANOVA found no significant difference between measurements (p >= 0.05). This means that the various reported concentrations appear to be within an acceptable variation of each other.
- Red: ANOVA found significant differences between measurements (p < 0.05). This means that the overall variation appears to be too large, at least one measurement appears to be out of line of the others.
Method described by Meert et al.
The measurement as proposed and used by Meert et al. (2) has been used to test for the reliability of reported concentration levels. By dividing the highest measurement by the lowest one, the result would put a concentration into 3 categories A, B and C. For results which were assigned to category C, an additional calculation was done by dividing the highest measurement by the mean concentration:
- A: Highest /Lowest <= 3.0: Minimal scatter, high reliability
- B: Highest /Lowest > 3.0 and < 8.5: Intermediate scatter, potential uncertainty of measurement.
- C: Highest /Lowest > 8.5: Substantial scatter, presumable uncertainty of measurement.
- D: Highest /Lowest > 8.5 and Highest /Mean > 5.5: High scatter, probable uncertainty of measurement.
All calculations are continuously updated meaning that newly entered data will lead to new means and variations for a specific solute.
Submitting new research data
The EUTox Database allows registered members to submit newly reported data. To become a registered member, please use the register link and fill out the form. Registration is manually approved and may take a few days to operate. Once you have been registered and provided with a login, you are able to submit data through the “Submit data” link located in the top menu.
Each submission must be supported by a Pubmed publication. For each solute, you can either submit a measured plasmatic concentration (from a healthy or uremic patient or patients) or provide a new clinical association, which should be at least part of the focus of the identified Pubmed publication. The submission is evaluated by members of the EUTox group, and either accepted or rejected. In any case, you will be notified about the decision by email. If your submission is accepted, the data will be permanently added to the Database and all calculations will include your data from that point on.
Publication and re-use
The Database is an original work from the European Uremic Toxins Work Group (EUTox) which aim is to provide information for re-use by other researchers. Researchers using the EUTox Database are invited to cite the Database as a source.
The citation of the Database should be:
The European Uremic Toxins (EUTox) Database. Available online at www.uremic-toxins.org, accessed on date.
The EUTox group welcomes your feedback and encourages researchers on uremia around the world to participate by sharing their data.
If you would like to contact the EUTox group, please refer to the instructions on our main website at www.uremic-toxins.org.
For technical problems and help on the database, please contact us at the email address firstname.lastname@example.org.
(1) Vanholder R, De Smet R, Glorieux G, Argilés A, Baurmeister U, Brunet P, et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934–43 ( Pubmed: 12675874 )
(2) Meert N, Schepers E, De Smet R, Argiles A, Cohen G, Deppisch R, et al. Inconsistency of reported uremic toxin concentrations. Artif Organs. 2007 Aug;31(8):600–11 ( Pubmed: 17651115 )
(3) Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol JASN. 2012 Jul;23(7):1258–70 ( Pubmed: 22626821 )
(4) Almeras C, Argilés A. The general picture of uremia. Semin Dial. 2009 Aug;22(4):329–33 ( Pubmed: 19708976 )