Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial

Christiane Ishikawa Ramos; Rachel Gatti Armani; Maria Eugenia Fernandes Canziani; Maria Aparecida Dalboni; Carla Juliana Ribeiro Dolenga; Lia Sumie Nakao; Katrina Louise Campbell; Lilian Cuppari

doi:10.1093/ndt/gfy171

Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial

Christiane Ishikawa Ramos, Rachel Gatti Armani, Maria Eugenia Fernandes Canziani, Maria Aparecida Dalboni, Carla Juliana Ribeiro Dolenga, Lia Sumie Nakao, Katrina Louise Campbell, Lilian Cuppari^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

66 Citations (Scopus)

Abstract

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 3 months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m²], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or placebo (maltodextrin, 12 g/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, 57.3 ± 14.6 years and eGFR 21.4 ± 7.6 mL/min/1.73 m²), 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 ΔPCS (treatment effect adjusted for baseline levels:-12.4 mg/L; 95% confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Δ%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 ΔPCS 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.

Original language	English
Pages (from-to)	1876-1884
Number of pages	9
Journal	Nephrology Dialysis Transplantation
Volume	34
Issue number	11
DOIs	https://doi.org/10.1093/ndt/gfy171
Publication status	Published - 1 Nov 2019

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10.1093/ndt/gfy171

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@article{b7860f4d36504ec0b7bead7692e10d9c,

title = "Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial",

abstract = "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 3 months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or placebo (maltodextrin, 12 g/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, 57.3 ± 14.6 years and eGFR 21.4 ± 7.6 mL/min/1.73 m2), 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 ΔPCS (treatment effect adjusted for baseline levels:-12.4 mg/L; 95% confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Δ%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 ΔPCS 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.",

author = "Ramos, {Christiane Ishikawa} and Armani, {Rachel Gatti} and Canziani, {Maria Eugenia Fernandes} and Dalboni, {Maria Aparecida} and Dolenga, {Carla Juliana Ribeiro} and Nakao, {Lia Sumie} and Campbell, {Katrina Louise} and Lilian Cuppari",

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doi = "10.1093/ndt/gfy171",

language = "English",

volume = "34",

pages = "1876--1884",

journal = "Nephrology Dialysis Transplantation",

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publisher = "OXFORD UNIV PRESS",

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Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial. / Ramos, Christiane Ishikawa; Armani, Rachel Gatti; Canziani, Maria Eugenia Fernandes et al.
In: Nephrology Dialysis Transplantation, Vol. 34, No. 11, 01.11.2019, p. 1876-1884.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial

AU - Ramos, Christiane Ishikawa

AU - Armani, Rachel Gatti

AU - Canziani, Maria Eugenia Fernandes

AU - Dalboni, Maria Aparecida

AU - Dolenga, Carla Juliana Ribeiro

AU - Nakao, Lia Sumie

AU - Campbell, Katrina Louise

AU - Cuppari, Lilian

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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 3 months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or placebo (maltodextrin, 12 g/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, 57.3 ± 14.6 years and eGFR 21.4 ± 7.6 mL/min/1.73 m2), 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 ΔPCS (treatment effect adjusted for baseline levels:-12.4 mg/L; 95% confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Δ%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 ΔPCS 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.

AB - 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 3 months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or placebo (maltodextrin, 12 g/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, 57.3 ± 14.6 years and eGFR 21.4 ± 7.6 mL/min/1.73 m2), 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 ΔPCS (treatment effect adjusted for baseline levels:-12.4 mg/L; 95% confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Δ%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 ΔPCS 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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U2 - 10.1093/ndt/gfy171

DO - 10.1093/ndt/gfy171

M3 - Article

C2 - 29939302

AN - SCOPUS:85074422811

SN - 0931-0509

VL - 34

SP - 1876

EP - 1884

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 11

ER -

Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial

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Nutrition for Chronic Disease and Disability: Research to improve health related quality of life and bring forward the under-represented voice

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Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial

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Nutrition for Chronic Disease and Disability: Research to improve health related quality of life and bring forward the under-represented voice

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