Abstract
Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.
Highlights
Chronic kidney disease (CKD) has emerged as a major public health concern that affects an estimated 37 million people in the United States [1,2]
The serum concentration of phenylacetylglutamine, a recently identified colonic microbial metabolite from amino acid fermentation, predicts the prevalence of cardiovascular diseases [51]. These findings provide a link between the multiple organ damage seen in CKD patients and gut microbiota-derived uremic toxins
Durning et al demonstrated that receptor for AGEs (RAGE) enhanced the inflammatory function of T cells, and that its increased levels in patients with type 1 diabetes may account for the chronic autoimmune response [97]
Summary
Chronic kidney disease (CKD) has emerged as a major public health concern that affects an estimated 37 million people in the United States [1,2]. Through the interaction with the receptor for AGEs (RAGE), AGEs promote further oxidative stress and stimulate several intracellular signaling molecules, leading to the production of inflammatory and profibrotic cytokines [14] Another uremic toxin, trimethylamine N-oxide (TMAO), which is a degradation product of choline and L-carnitine, is shown to accumulate when renal function declines and correlates with enhanced cardiovascular mortality in CKD patients [15,16]. Understanding the mutual relationship between gut microbiota dysbiosis and uremic toxins such as AGEs and TMAO is of great importance for preventing kidney injury and developing new therapeutic options for CKD patients. This review highlights the underlying mechanisms by which the reciprocal regulation of gut microbiota dysbiosis and uremic toxins drives CKD progression
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