Effects of prebiotic (fructooligossacharide) on uremic toxins in patients with chronic kidney disease

• Grant number: 14/20725-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2015
• Effective date (End): June 30, 2018
• Field of knowledge: Health Sciences - Nutrition
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Lilian Cuppari
• Grantee: Christiane Ishikawa Ramos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 16/19724-7 - Effect of a prebiotic (fructooligosacharide) on uremic toxins of chronic kidney disease patients, BE.EP.DR

Abstract

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, cardiovascular dysfunction and increased risk of death in this population of patients. Besides restriction of dietary protein, a well-established therapy for reducing uremic toxicity, other dietary approaches such as the use of prebiotics, probiotics and symbiotics may represent a promising intervention due to their beneficial effect as modulators of the intestinal microbiota. Preliminary short-term studies with patients undergoing dialysis have shown that such intervention promoted reduction in the serum concentration of p-cresyl sulfate or indoxyl sulfate. Due to the diversity of agents with prebiotic and probiotic activities and the several possible combinations, the superiority between them has not yet been established. In comparison to probiotics, prebiotics 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 (frutooligoschadaride -FOS) on serum and urinary levels of p-cresyl sulfate and indoxyl sulfate of non-dialysis dependent patients with CKD. As a secondary aim we will investigate the impact of such intervention on 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-cresil sulfate and indoxil sulfate will be determined by high performance liquid chromatography (HPLC). The serum markers of intestinotrophic effect (glucagon-like peptide 2 - GLP2 - and epidermal growth factor - EGF), intestinal permeability (Zonulina), 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. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RAMOS, CHRISTIANE ISHIKAWA; ARMANI, RACHEL GATTI; CANZIANI, MARIA EUGENIA; DOLENGA, CARLA JULIANA RIBEIRO; NAKAO, LIA SUMIE; CAMPBELL, KATRINA LOUISE; CUPPARI, LILIAN. Bowel Habits and the Association With Uremic Toxins in Non-Dialysis-Dependent Chronic Kidney Disease Patients. JOURNAL OF RENAL NUTRITION, v. 30, n. 1, p. 31-35, JAN 2020. (16/19724-7, 14/20725-2)