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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #307749
Title: A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

Author
item VAZIRI, NOSRATOLA - University Of California
item LIU, SHUMAN - University Of California
item LAU, WEI LING - University Of California
item KHAZAEIL, MAHYAR - University Of California
item NAZER-TEHRANI, SOHRAB - University Of California
item FARZANEH, SEYED - University Of California
item KEIFFER, DOROTHY - University Of California
item Adams, Sean
item MARTIN, ROY - University Of California

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2014
Publication Date: N/A
Citation: N/A

Interpretive Summary: Unhealthy kidney function leading to or associated with chronic kidney disease (CKD) is associated with a pro-inflammatory environment, and can be exacerbated by an inability to handle the body’s nitrogen load from metabolism of proteins and amino acids. Dietary interventions that can thwart CKD development or severity are of interest, especially in terms of those food components that can reduce inflammation, help balance nitrogen and fluid load on the body, and help maintain good renal health. CKD is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2- disruption of epithelial barrier by urea-derived ammonia and ammonium hydroxide leading to endotoxemia and bacterial translocation; and 3- restriction of potassium-rich fruits and vegetables which are common sources of dietary fermentable fiber such as resistant starch. Restriction of these foods leads to depletion of bacteria that can convert indigestible carbohydrates to short chain fatty acids (SCFA) which are important nutrients for colonocytes and anti-inflammatory immune cells. We therefore tested the hypothesis that consumption of a high resistant starch diet attenuates oxidative stress, inflammation, and CKD progression. Methods- Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce chronic interstitial nephropathy. Rats were then fed semi-purified diets supplemented with amylopectin (low-fiber control) or a high fermentable fiber diet containing 59% amylose maize resistant starch (HAM-RS2) for 3 weeks. Results- The CKD rats consuming the low fermentable fiber diet exhibited impaired urinary concentrating capacity, reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, and down-regulation of antioxidant enzymes. The high resistant starch diet significantly attenuated these abnormalities. Conclusions- High resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in a rat model of CKD. Future studies are needed to explore the impact of HAM-RS2 and other forms of fiber that can modify the intestinal environment and microflora, on modifying kidney health and reducing kidney disease in humans.

Technical Abstract: Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2- disruption of epithelial barrier by urea-derived ammonia and ammonium hydroxide leading to endotoxemia and bacterial translocation; and 3- restriction of potassium-rich fruits and vegetables which are common sources of dietary fermentable fiber such as resistant starch. Restriction of these foods leads to depletion of bacteria that can convert indigestible carbohydrates to short chain fatty acids (SCFA) which are important nutrients for colonocytes and anti-inflammatory regulatory T lymphocytes. We therefore tested the hypothesis that consumption of a high resistant starch diet attenuates oxidative stress, inflammation, and CKD progression. Methods- Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce chronic interstitial nephropathy. Rats were then fed semi-purified diets supplemented with amylopectin (low-fiber control) or a high fermentable fiber diet containing 59% amylose maize resistant starch (HAM-RS2) for 3 weeks. Results- The CKD rats consuming the low fermentable fiber diet exhibited impaired urinary concentrating capacity, reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, and down-regulation of antioxidant enzymes. The high resistant starch diet significantly attenuated these abnormalities. Conclusions- High resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats with adenine-induced CKD. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.