Prebiotic in Chronic Kidney Disease Patients
- Conditions
- Chronic Kidney Disease
- Interventions
- Dietary Supplement: FructooligosaccharideDietary Supplement: Maltodextrin
- Registration Number
- NCT02364869
- Lead Sponsor
- Federal University of São Paulo
- Brief Summary
This 12-week double-blind randomized controlled clinical trial aims to investigate the effect of a prebiotic (fructooligosaccharide - FOS) on serum and urinary levels of uremic toxins (p-cresyl sulfate and indoxyl sulfate) of non-dialysis dependent CKD patients, and the impact of such intervention on cardiovascular markers, intestinal permeability, endotoxemia and inflammatory response.
- Detailed Description
Intestinal microbiome has been considered a new therapeutic target for chronic kidney disease (CKD) due to its potential role on the metabolic disturbances associated to the disease. The abnormalities in the microbiota, frequently found in patients with CKD, contribute to the accumulation of uremic toxins derived from the unbalanced fermentation of nitrogen compounds in relation to the non-digestible carbohydrates. Among them, p-cresyl sulfate and indoxyl sulfate have been associated with inflammation, kidney disease progression, endothelial dysfunction and increased risk of death in this population. Preliminary studies especially on hemodialysis have shown that the use of prebiotic, probiotic and symbiotic may represent a promising intervention due to their beneficial effect as modulators of the intestinal microbiota that might promote a reduction on serum concentration of p-cresyl sulfate and indoxyl sulfate. In comparison to probiotic, prebiotic have the advantage to stimulate the host's microbiota and to occur naturally in several foods. In the context of CKD, the use of prebiotics has been poorly investigated. Therefore, the primary aim of this study is to investigate the effect of a prebiotic (fructooligosaccharide - FOS) on serum and urinary levels of p-cresyl sulfate and indoxyl sulfate of non-dialysis dependent CKD patients. As a secondary aim we will investigate the impact of such intervention on cardiovascular markers, intestinal permeability, endotoxemia and inflammatory response. This is a 12-week double-blind randomized controlled clinical trial. Fifty non-diabetic patients with CKD stages 3a and 4 will be randomly assigned to a 12 g/day of FOS or maltodextrin (placebo). The serum and urinary concentrations of p-cresyl sulfate and indoxyl sulfate will be determined by high performance liquid chromatography (HPLC). The assessment of endothelial function includes ultrasonography of the brachial artery, measurement of plasma and urinary nitric oxide, monocyte chemoattractant protein 1 (MCP1), stromal cell-derived factor 1 alpha (SDF1α), oxide - trimethylamine N- (TMAO), ambulatory blood pressure monitoring (ABPM) and pulse wave velocity (PWV). The serum intestinal trophic markers (glucagon-like peptide 2 - GLP2 - and epidermal growth factor - EGF), intestinal permeability (Zonulin), endotoxemia and inflammation (IL-6 and CRP) will be determined by ELISA. Food intake will be assessed by 3-day food records. Protein intake will be estimated by calculating the protein equivalent of nitrogen appearance (PNA). The Bristol Scale, the Roma III Criteria and the Gastrointestinal Symptoms Rating Scale will be applied to evaluate gastrointestinal effects during the follow-up. The subjective global assessment questionnaire, the spectroscopic bioimpedance analysis and the handgrip strength will be applied to evaluate the nutritional status of the patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- 18 to 80 years
- Estimated glomerular filtration rate between 45 to 15 ml/min/1,73m².
- diabetes mellitus, malignance, severe liver disease, autoimmune diseases, congestive heart failure class III / IV, HIV, history of gastrointestinal disease
- use of phosphate binders, laxatives or prebiotic, probiotic, symbiotic, antibiotics, immunosuppressants and / or anti-inflammatory drugs three months preceding the study.
- patients using laxatives who refuse to stop treatment during the follow-up
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fructooligosaccharide Fructooligosaccharide 12g daily, for 12 weeks Maltodextrin Maltodextrin 12g daily, for 12 weeks
- Primary Outcome Measures
Name Time Method Uremic toxicity evaluated by serum and urinary levels of p-cresyl sulfate and indoxyl sulfate 12 weeks
- Secondary Outcome Measures
Name Time Method Endotoxemia measured by serum levels of lipopolysaccharides 12 weeks Endothelial function evaluated by blood pressure monitoring (ABPM) 12 weeks Endothelial function evaluated by plasma and urinary levels of monocyte chemoattractant protein 1 (MCP1) 12 weeks Intestinal permeability evaluated by serum levels of Zonulin 12 weeks Intestinal epithelium evaluated by serum levels of epidermal growth factor (EGF). 12 weeks Inflammation measured by serum levels of Interleukin-6 (IL-6) 12 weeks Inflammation measured by serum levels of c-reactive protein (CRP) 12 weeks Endothelial function evaluated by plasma and urinary levels of oxide - trimethylamine N- (TMAO) 12 weeks Endothelial function evaluated by ultrasonography of the brachial artery 12 weeks Intestinal epithelium evaluated by serum levels of glucagon-like peptide 2 (GLP2) 12 weeks Endothelial function evaluated by pulse wave velocity (PWV). 12 weeks Endothelial function evaluated by plasma and urinary levels of nitric oxide 12 weeks Endothelial function evaluated by plasma and urinary levels of stromal cell-derived factor 1 alpha (SDF1α) 12 weeks
Trial Locations
- Locations (1)
Federal University of São Paulo
🇧🇷São Paulo, Brazil