A guide to uraemic toxicity.

When kidney function is compromised, myriad metabolites and peptides - uraemic retention molecules (URMs) - accumulate in the body and compromise homeostasis. Over 150 molecules have been classified as URMs but omics approaches are revealing many more. When URMs exert pathophysiological effects and/or are associated with relevant adverse patient outcomes, they are called uraemic toxins. The origins of uraemic toxins and their contributions to post-translational modification of proteins are important current areas of research. Although most research has thus far focused on uraemic toxins, new studies have also identified URMs with the potential to counteract harmful biological changes that might thus confer a beneficial effect. To tackle the growing burden of chronic kidney disease, preventive therapeutic measures must target the disease early in its course and a balanced view of uraemic retention is needed to understand the role of URMs in kidney disease progression. Knowledge of the origin of the solutes, their kinetics, context-dependent biological profile and the involvement of transporter-mediated interorgan communication by small molecules - termed 'remote sensing and signalling' - is indispensable to facilitate the development of interventions that can promote or restore homeostasis in people with kidney dysfunction.