益生元（果寡糖）对慢性肾脏病患者尿毒症毒素的影响：一项随机对照试验。

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

机构信息

Nutrition Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

Hospital do Rim - Fundação Oswaldo Ramos, São Paulo, Brazil.

出版信息

Nephrol Dial Transplant. 2019 Nov 1;34(11):1876-1884. doi: 10.1093/ndt/gfy171.

DOI:10.1093/ndt/gfy171

PMID:29939302

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.

摘要

背景

微生物来源的尿毒症毒素，对甲酚硫酸盐（PCS）、吲哚硫酸酯（IS）和吲哚 3-乙酸（IAA），与慢性肾脏病（CKD）的负担有关。益生元作为一种替代方法，已经出现以调节肠道环境并减轻毒素产生。本试验旨在研究一种益生元低聚果糖（FOS）对非透析依赖型慢性肾脏病（NDD-CKD）患者尿毒症毒素的影响。

方法

进行了为期 3 个月的双盲、安慰剂对照、随机试验。共有 50 名非糖尿病性 NDD-CKD 患者[估计肾小球滤过率（eGFR）<45 mL/min/1.73 m2]，年龄 18-80 岁，被分配到益生元（FOS，12 g/天）或安慰剂（麦芽糊精，12 g/天）组。主要结局是血清（总和游离）和尿液（总）PCS 的变化。次要结局包括 IS、IAA、肠道通透性（肠联蛋白）血清标志物、肠道营养因子（表皮生长因子和胰高血糖素样肽-2）、eGFR、炎症（高敏 C 反应蛋白和白细胞介素-6）、稳态模型评估-胰岛素抵抗、血脂谱和胃肠道症状的变化。

结果

从 50 名参与者（54%为男性，57.3±14.6 岁，eGFR 21.4±7.6 mL/min/1.73 m2）中，有 46 名完成了随访。未观察到饮食摄入或胃肠道症状的变化。血清总 ΔPCS（调整基线水平的治疗效果：-12.4 mg/L；95%置信区间[-5.6 至 0.9 mg/L；P=0.07）和血清游离 Δ%PCS[干预组-8.6（-41.5 至 13.9%）与安慰剂组 3.5（-28.8 至 85.5%）；P=0.07]之间存在差异的趋势。血清总 ΔPCS 的这种趋势与 eGFR 和饮食蛋白质：纤维比值的摄入无关。两组间尿液 PCS 无差异。除干预组高密度脂蛋白胆固醇降低外，两组间 IS、IAA 或其他次要结局的变化均无差异。