Chronic kidney disease and gut microbiota

Abstract

Chronic kidney disease (CKD) refers to a range of various pathophysiological processes correlated with abnormal renal function and a progressive loss in GFR. Just as dysbiosis and altered pathology of the gut are accompanied with hypertension, which is a significant CKD risk factor. Gut dysbiosis in CKD patients is associated with an elevated levels of uremic toxins, which in turn increases the CKD progression. According to research results, the gut-kidney axis has a role in the formation of kidney stones, also in IgAN. A number of researchers have categorized the gut microbiota as enterotypes, and others, skeptical of theory of enterotypes, have suggested biomarkers to describe taxa that related to lifestyle, nutrition, and disease status. Metabolome-microbiome studies have been used to investigate the interactions of host-gut microbiota in terms of the involvement of metabolites in these interactions and are yielded promising results. The correlation between gut microbiota and CKD requires further multi-omic researches. Also, with regard to systems biology, studies on the communication network of proteins and transporters such as SLC and ABC, can help us achieve a deeper understanding of the gut-liver-kidney axis communication and can thus provide promising new horizons in the treatment of CKD patients. Probiotic-based treatment is an approach to reduce uremic poisoning, which is accomplished by swallowing microbes those can catalyze URS in the gut. If further comprehensive studies are carried out, we will know about the probiotics impact in slowing the renal failure progression and reducing inflammatory markers.

Keywords: Chronic kidney disease; Glomerular filtration rate; Gut microbiota; Renal failure.

Fig. 1

Blood urea levels raise and urea influx to gut lumen in CKD patients. Dysbiosis of gut microbiota increases some of urease containing bacteria and urease activity increases ammonium hydroxide. On the otherhand the low fiber diet of these patients decreases SCFAs production by gut bacteria which are the colonocytes nutrients. The SCFAs decrease together with ammonium hydroxide increase, damage to intestinal epithelium barrier (tight junctions) and then uremic toxins and bacterial derivatives such as endotoxins penerate from damaged epithelium and entered to blood circulation and cause to inflammatory and oxidative processes such as CVD and CKD. SCFA: Short chain fatty acid; CVD: Cardiovascular disease; CKD: Chronic kidney disease.

Fig. 2

The relationship of gut dysbiosis and chronic kidney disease stages. Left: Vicious circuit that theoretically impact in health status of kidney. Kidney failure cause an increase in blood urea levels, then urea influxes to gut lumen and alters gut microbiota (dysbiosis), this condition increases uremic toxins and NH4OH and these toxins damage to gut epithelial tight junction which increases permeability of gut barrier and then uremic toxins and bacterial derivatives such as endotoxins translocate to blood circulation and damage to organs such as heart and kidney. Right: The stages of chronic kidney disease according to GFR. CKD: Chronic kidney disease; CVD: Cardiovascular disease; GFR: Glomerular filtration rate; ESRD: End stage renal disease.