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.

An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of b2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD. The uremic syndrome is characterized by the retention of various solutes that would normally be excreted by the kidneys. The substances that interact negatively with biologic functions are called uremic toxins. In the past years, research on uremic toxicity has been very dynamic and resulted in the identification of dozens of retention solutes, including several uremic toxins. In 2003, the European Uremic Toxin Work Group (http://www.uremic-toxins.org/) proposed a classification of 90 retention solutes providing data on normal and pathologic serum concentrations. 1 In 2007, results were further discussed and expanded with the addition of 14 solutes. 2,3 This collaborative work focused on the highest mean or median concentration of the solutes measured in a uremic population and the highest individual uremic concentration. These data were particularly relevant for researchers on uremic toxicity, and they became a successful tool for allowing use of standardized and biologically relevant concentrations in experimental settings. More recently, scientific and technological progress resulted in the identification of many new uremic retention solutes, particularly thanks to nontargeted approaches such as metabolomic and proteomic profiling. 4,5 To maintain experimental guidelines in keeping with current knowledge, it seemed necessary to propose an update of the encyclopedic review.

Urea and creatinine are far more efficiently removed than the other compounds under study, except for hippuric acid. There are no striking differences between the HF membranes. Moreover, compared with the LF membrane these HF membranes do not appear to be superior in removing the studied compounds.

Inflammatory bowel diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome, mucus layer composition and immune factors in conventional mice. We compared smoke-exposed with air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure. Interestingly, an increase of Lachnospiraceae sp. activity in the colon was observed. Also, the mRNA expression of Muc2 and Muc3 increased in the ileum, whereas Muc4 increased in the distal colon of smoke-exposed mice (n = 6). Furthermore, we observed increased Cxcl2 and decreased Ifn-γ in the ileum, and increased Il-6 and decreased Tgf-β in the proximal colon. Tight junction gene expression remained unchanged. We infer that the modulating role of chronic smoke exposure as a latently present risk factor in the gut may be driven by the altered epithelial mucus profiles and changes in microbiome composition and immune factors.

The retention in the body of compounds, which normally are secreted into the urine results in a clinical picture, called the uremic syndrome. The retention compounds responsible for the uremic syndrome are called uremic toxins. Only a few of the uremic retention solutes fully conform to a true definition of uremic toxins. Uremic patients develop atheromatotic vascular disease more frequently and earlier than the general population. The classical risk factors seem to be less important. Other factors have been suggested to be at play, and among those uremic toxins are mentioned as potential culprits. The identification, classification and characterization of the solutes responsible for vascular problems seems of utmost importance but is far from complete due to a lack of standardization and organization. The European Uremic Toxin Work Group (EUTox) has as a primary aim to discuss, analyze and offer guidelines in matters related to the identification, characterization, analytical determination and evaluation of biological activity of uremic retention solutes. The final aim remains the development of new strategies to reduce the concentration of the most active uremic solutes. These activities will at first be concentrated on reducing factors influencing cardiovascular morbidity and mortality.