Intestinal barrier dysfunction in chronic kidney disease: evidence, mechanisms, and its potential clinical...

The gut-kidney axis plays a critical role in chronic kidney disease (CKD), with evidence suggesting that intestinal barrier dysfunction contributes to systemic inflammation and toxin accumulation. However, findings remain inconsistent due to heterogeneous study designs and outcome measures. This scoping review systematically assessed experimental and clinical evidence on gut permeability in CKD and identified gaps in current knowledge. We searched Embase, PubMed, Web of Science, Cochrane Library, and Scopus (March 2024; updated June 2025) using a protocol registered on the Open Science Framework. Eligible studies investigated intestinal barrier function in CKD with a control group. Two reviewers screened records, assessed risk of bias with the Office of Health Assessment and Translation tool, and extracted data on permeability markers, tight junction proteins (TJPs), and related outcomes. Of 10 661 records screened, 143 studies were included: 6 in vitro, 93 animal, 36 human, and 8 papers with a combination of study types. In vitro models showed increased permeability after exposure to uremic toxins, although effects on TJP expression were inconsistent. Animal models demonstrated impaired barrier function as assessed by Fluorescein isothiocyanate-dextran, reduced transepithelial electrical resistance, and decreased expression of the TJPs. Human studies reported elevated biomarkers of permeability in advanced CKD and dialysis, while early-stage disease showed variable results. Limited human data indicated reduced occludin expression. Associations between gut permeability, systemic inflammation, gastrointestinal symptoms, sarcopenia, and kidney outcomes were observed, but remain preliminary. Interpretation of the results should consider the high level of bias and the lack of power calculations in both the in vitro and animal data. Current evidence supports impaired intestinal barrier function in CKD, particularly in advanced stages. However, study heterogeneity and frequent risk of bias limit firm conclusions. Standardized methods and longitudinal clinical studies are needed to clarify the role of gut permeability in CKD progression and to evaluate whether barrier-targeted interventions may improve outcomes.