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为期10个月的合生元摄入对非透析慢性肾病患者估算肾小球滤过率、尿毒症毒素、氧化应激和炎症标志物的影响:一项前瞻性、非随机、安慰剂对照研究

The Impact of a 10-Month Synbiotic Intake on eGFR, Uremic Toxins, Oxidative Stress, and Inflammatory Markers in Non-Dialysis Chronic Kidney Disease Patients: A Prospective, Non-Randomized, Placebo-Controlled Study.

作者信息

Kuskunov Teodor, Tilkiyan Eduard, Zdravkova Irina, Valova Siyana, Boyanov Krasimir, Bivolarska Anelia

机构信息

Department of Propaedeutics of Internal Diseases, Medical Faculty, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria.

Hemodialysis Unit, University Hospital "Kaspela", 4000 Plovdiv, Bulgaria.

出版信息

Medicina (Kaunas). 2025 Jun 30;61(7):1199. doi: 10.3390/medicina61071199.

DOI:10.3390/medicina61071199
PMID:40731829
Abstract

: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV-V CKD not receiving dialysis, in comparison to placebo. : Fifty non-dialysis CKD IV-V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing La-14 (2 × 10 CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. : Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was -1.2 ± 2.5 mL/min/1.73 m (synbiotic) vs. -3.5 ± 3.0 mL/min/1.73 m (placebo); between-group difference in change was 2.3 mL/min/1.73 m (95% CI: 0.5-4.1; = 0.014; adjusted = 0.07). IS decreased by -15.4 ± 8.2 ng/L vs. -3.1 ± 6.5 ng/L; between-group difference in change was -12.3 ng/L (95% CI: -17.8 to -6.8; < 0.001; adjusted = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. : Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management.

摘要

慢性肾脏病(CKD)在全球范围内的患病率持续上升,这是公共卫生系统面临的一个主要问题。CKD与肠道微生物群失调有关,肠道微生物群失调可能通过增加尿毒症毒素水平、全身炎症和氧化应激来加剧疾病进展。通过生物制剂补充来调节肠道微生物群已被提议作为减缓CKD进展和减轻其并发症的一种潜在治疗策略。本研究旨在评估为期10个月的合生元补充剂对未接受透析的IV-V期CKD患者的估计肾小球滤过率(eGFR)、硫酸吲哚酚(IS)、对甲酚硫酸盐(p-CS)、白细胞介素-6(IL-6)和丙二醛(MDA)循环浓度的影响,并与安慰剂进行比较。

50例非透析CKD IV-V期患者通过匹配的非随机分配(年龄、性别和原发性疾病)分为合生元组或安慰剂组(每组n = 25)。这项单盲、安慰剂对照试验对参与者和实验室人员设盲。合生元组每天服用含有La-14(2×10CFU/g)+低聚果糖的胶囊;对照组服用相同的安慰剂。每月监测依从性(药丸计数、日记),两次就诊依从性<80%则退出。在基线和第10个月时测量eGFR、IS、p-CS、IL-6和MDA。

42例患者(每组21例)完成了研究;8例退出(每组4例)。在10个月时,eGFR的变化为-1.2±2.5 mL/min/1.73m²(合生元组) vs. -3.5±3.0 mL/min/1.73m²(安慰剂组);组间变化差异为2.3 mL/min/1.73m²(95%CI:0.5-4.1;P = 0.014;校正后P = 0.07)。IS下降了-15.4±8.2 ng/L,而安慰剂组下降了-3.1±6.5 ng/L;组间变化差异为-12.3 ng/L(95%CI:-17.8至-6.8;P<0.001;校正后P = 0.005)。校正后,p-CS、IL-6或MDA未观察到显著差异。

为期10个月的合生元补充剂导致晚期CKD患者血清IS水平有下降趋势,提示针对微生物群的治疗可能有益。然而,对肾功能、炎症或氧化应激标志物未观察到显著影响。需要进一步的大规模研究来证实这些发现,并探索合生元在CKD管理中的长期影响。

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本文引用的文献

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Efficacy of probiotics/synbiotics supplementation in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.补充益生菌/合生元对慢性肾病患者的疗效:一项随机对照试验的系统评价和荟萃分析
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