Abstract
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.
Highlights
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression
Among factors potentially impacting on microbiota composition, we find diet changes, prescribed drugs, accumulation of toxins that may alter the gut microenvironment and the impaired immune response which may disturb the host:microbiota interaction and lead to repetitive antibiotic courses
Uremic toxins originating in the microbiota that have been linked in epidemiological studies and preclinical interventional studies to CKD progression include p-cresyl sulphate (pCS) and pCG, indoxyl sulphate (IS) and indole-3 acetic acid (IAA) and trimethylamine N-Oxide (TMAO)
Summary
Around 10% of the adult population has chronic kidney disease (CKD), which is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2 or the urinary. Toxins 2018, 10, 300 albumin:creatinine ratio (UACR) rises above 30 mg/g or there is other evidence of kidney injury, for more than 3 months, even in the presence of normal GFR [1].The thresholds for eGFR and albuminuria are not arbitrary: they signal the point when kidney injury results in both a higher risk of death and in a higher risk of CKD progression to end-stage kidney disease (ESKD) [2,3]. Accumulation of uremic toxins has been considered a key contributor to the consequences of CKD when eGFR is
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
