LAUSR

When kidney functions fail (chronic kidney disease—CKD), this results in a diminished urinary excretion and thus retention of waste products of metabolism and a gradual decline of almost every function of the body. This process is attributed to an endogenous intoxication by these accumulated metabolites. This emanates in a clinical picture that is called “uremic syndrome,” a term interchangeably used with “uremia” and referring to the most abundant and also first recognized retention product, urea. In as far as elements of the clinical picture are caused by the biological or biochemical action of these retained metabolites, the latter are called “uremic toxins,” and their consequence is “uremic toxicity.” The clinical picture emanating from this uremic syndrome as well as the mechanisms leading to it are complex and multifactorial. Major patho-physiologic mechanisms at play are inflammation, protein energy wasting, disturbed glucose handling, dysfunction of vascular cells, thrombogenesis, and fibrosis, but the list of baseline mechanisms is far more extensive [1]. The leading organ dysfunction and a major cause of death in CKD patients is cardiovascular disease [2], but in this respect, the picture is more exhaustive, comprising susceptibility to infection, gastro-intestinal dysfunction, inadequate handling of metabolites, and neural conduction disturbances [1]. A newly detected and likely important contributor is the role played in uremic toxin generation by the intestine and the intestinal microbiome [3,4] that affects and is affected by the uremic status. The knowledge of uremic toxicity (as well of the responsible retention products, of their retention pattern as of their toxic effects) has been growing exponentially over the last decades, in part stimulated by the publication of encyclopedic uremic toxin lists [5,6], the novel possibilities raised by the refinement of comprehensive “omic” approaches [7,8], and the creation of collaborative work groups focusing on uremic toxicity such as the European Uremic Toxin Work Group (EUTox) [9]. In the slipstream of our increasing knowledge of the components exerting uremic toxicity, and as a consequence of the increasing possibilities of biochemistry and molecular biology, also our understanding of the mechanisms at the origin of uremic toxicity has been growing. In this context, it was decided in 2015–2016 that the journal Toxins would publish a special issue on uremic toxicity that would be devoted to the novel uremic toxins, either newly detected molecules, or well-known solutes with newly detected biological effects. Focus could be as well on identification, biologic effects, generation as on removal or other approaches to decrease concentration. It is the intention of this editorial to summarize the content of the 15 publications contained in this special issue. To reach this aim, toxins will be discussed according to the currently used classification system, i.e., small water-soluble compounds, protein bound compounds and middle molecules (Table 1). Table 1 Articles contained in the special issue on “novel uremic toxins.”