Abstract
Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.
Highlights
Systemic inflammation and oxidative stress play central roles in progression of chronic kidney disease (CKD) and the associated complications
Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber
Recent studies have revealed that advanced CKD results in disruption of the gastro-intestinal epithelial barrier structure and function [1,2,3] and profound changes in the composition and function of the intestinal microbiota [4, 5], events that contribute to the pathogenesis of systemic inflammation
Summary
Systemic inflammation and oxidative stress play central roles in progression of chronic kidney disease (CKD) and the associated complications. Chief among them is the rise in urea concentration in the body fluids which leads to its heavy influx into the gastrointestinal tract, where it accommodates the dominance of urease-possessing bacteria, conversion of urea to ammonia [NH2-CO-NH2+H2OR 2NH3+CO2] and formation of ammonium hydroxide [NH3+H2O RNH4(OH)] These caustic products, in turn, damage the tight junction proteins that face the lumen and seal the gap between the epithelial cells [6, 7]. The other likely cause of the altered intestinal microbiome is dietary restriction of potassium-rich fruits and vegetables (to prevent hyperkalemia) which are common sources of soluble and insoluble dietary fiber These indigestible complex carbohydrates are the primary source of nutrients for the symbiotic intestinal bacteria that convert the dietary fiber to short chain fatty acids (SCFA). The T-reg cell population is markedly reduced in endstage renal disease (ESRD) patients [13, 14] and recent studies have shown marked reduction of SCFA-producing bacterial families in these patients [5]
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