Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 34, Issue 11, Pages 1876-1884Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfy171
Keywords
chronic kidney disease; indoxyl sulfate; p-cresyl sulfate; prebiotic; uremic toxins
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
- Hospital do Rim - Fundacao Oswaldo Ramos (Sao Paulo, Brazil)
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Background Microbial-derived uremic toxins, p-cresyl sulfate (PCS), indoxyl sulfate (IS) and indole 3-acetic acid (IAA), have been associated with the burden of chronic kidney disease (CKD). Prebiotics have emerged as an alternative to modulate the gut environment and to attenuate toxin production. This trial aims to investigate the effect of a prebiotic fructooligosaccharide (FOS) on uremic toxins of non-dialysis-dependent CKD (NDD-CKD) patients. Methods A double-blind, placebo-controlled, randomized trial was conducted for 3months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR)<45mL/min/1.73m(2)], aged 18-80years, were allocated to prebiotic (FOS, 12g/day) or placebo (maltodextrin, 12g/day) groups. Primary outcomes were changes in serum (total and free) and urinary (total) PCS. Secondary outcomes included changes in IS, IAA, serum markers of intestinal permeability (zonulin), gut-trophic factors (epidermal growth factor and glucagon-like peptide-2), eGFR, inflammation (high sensitive c-reactive protein and interleukin-6), homeostatic model assessment-insulin resistance, lipid profile and gastrointestinal symptoms. Results From 50 participants (54% men, 57.314.6years and eGFR21.4 +/- 7.6mL/min/1.73m(2)), 46 completed the follow-up. No changes in dietary intake or gastrointestinal symptoms were observed. There was a trend in the difference of serum total Delta PCS (treatment effect adjusted for baseline levels: -12.4mg/L; 95% confidence interval (-5.6 to 0.9mg/L; P=0.07) and serum-free Delta%PCS [intervention -8.6 (-41.5 to 13.9%) versus placebo 3.5 (-28.8 to 85.5%); P=0.07] between the groups. The trend in the difference of serum total Delta PCS was independent of eGFR and dietary protein:fiber ratio intake. No difference was found in urinary PCS. Aside from the decreased high-density lipoprotein cholesterol in the intervention, no differences were observed in the change of IS, IAA or other secondary outcome between the groups. Conclusions Our result suggests the potential of FOS in reducing serum total and free PCS in nondiabetic NDD-CKD patients.
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