Prebiotic in Chronic Kidney Disease Patients
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional

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.
    

Intervention name(s): Fructooligosaccharide; Maltodextrin
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Patients will be evaluated at baseline, week 6 and 12.; Placebo Comparator. Patients will be evaluated at baseline, week 6 and 12.
Other intervention name(s): Prebiotic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: P-cresyl sulfate; Indoxyl sulfate; Intestine; Endothelial function