Effect of the Gut Microbiome on the reduction of uremic toxins in patients with chronic kidney disease: A systematic review & Network meta-analysis

Abstract

Introduction Chronic kidney disease (CKD) is associated with increased intestinal barrier permeability, leading to heightened inflammation and oxidative stress. These changes contribute to complications such as cardiovascular disease, anemia, altered mineral metabolism, and CKD progression. Interventions using prebiotics, probiotics, and synbiotics may help mitigate dysbiosis and improve intestinal barrier function.

Aim This study conducted a network meta-analysis to evaluate the effectiveness of probiotics, prebiotics, and synbiotics in reducing uremic toxins produced by the gut microbiota in CKD patients.

Method A systematic review and network meta-analysis of randomized clinical trials (RCTs) was performed. The analysis focused on the use of prebiotics, probiotics, and synbiotics in CKD patients at stages 3 to 5, as per KDIGO guidelines, and their association with reductions in uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), urea, and creatinine. The study follows the PRISMA statement.

Results The studies included 331 patients, primarily male, across CKD stages 3a to 5. The interventions showed a positive impact on the gut microbiota composition, leading to reductions in both free and total p-cresyl sulfate and indoxyl sulfate.

Conclusion The findings suggest that modulating the gut microbiota through these interventions can effectively reduce specific uremic toxins. However, further trials are necessary to better understand the microbiota modulation and its impact on intestinal bacterial composition.

PROSPERO Registration CRD42023438901

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The author(s) received no specific funding for this work.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The manuscript is registered with PROSPERO under the registration number CRD42023438901, ensuring that the systematic review and network meta-analysis were conducted following a pre-specified protocol, which enhances the transparency and reliability of the research findings

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

All relevant data are within the manuscript and its Supporting Information files

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