Decreasing microbiota-derived uremic toxins to improve CKD outcomes

Chronic kidney disease (CKD) is set to become the fifth-leading global cause of death by 2040. This illustrates the many unknowns regarding its pathogenesis and therapy. A key unknown relates to the therapeutic impact of the interaction between CKD and the gut microbiome. The normal gut microbiome is essential for body homeostasis. There is evidence for multiple interactions between the microbiota and CKD—its causes, comorbidities and therapeutic interventions—that are only starting to be unraveled. Thus uremic retention products, such as urea itself, modify the gut microbiota biology and both dietary and drug prescriptions modify the composition and function of the microbiota. Conversely, the microbiota may influence the progression and manifestations of CKD through the production of biologically active compounds (e.g. short-chain fatty acids such as butyrate and crotonate) and precursors of uremic toxins. The present review addresses these issues and their relevance for novel therapeutic approaches ranging from dietary interventions to prebiotics, probiotics, synbiotics and postbiotics, to the prevention of the absorption of microbial metabolites and to increased clearance of uremic toxins of bacterial origin through optimized dialysis techniques or blockade of tubular cell transporters.