Abstract Background and Aims Patients with chronic kidney disease (CKD) present evidence of systemic inflammation without clinical infection. This is partly attributed to intestinal barrier dysfunction resulting in increased gut permeability with microbial and endotoxin translocation. However, the potential mechanism(s) implicated in increased gut permeability remain unclear. In this study, we investigated several parameters of the intestinal barrier in patients with CKD of various stages. Methods Thirty-three patients with CKD were prospectively enrolled. Patients were divided in stage I-IV CKD (group A, n = 17, 9 of them with IgA nephropathy) or end-stage kidney disease (ESKD) (group B, n = 16) and were compared with 11 healthy controls (group C). Duodenal biopsies from all subjects, obtained by endoscopy, were examined histologically for evaluation of the villous length and apoptotic bodies in cryptal epithelium. Intraepithelial CD3+ T-lymphocytes, expression of occludin and claudin-1 in the intestinal epithelium were evaluated by immunohistochemistry. Circulating endotoxin concentration was measured by enzyme-linked immunosorbent assay and cytokine levels [interleukin (IL)-1β, IL-6, IL-8, IL-10, TNF-a] by flow cytometry. Results Patients in groups A and B presented significantly higher serum endotoxin, IL-8 and IL-10 levels compared to controls (p<0.01, both groups). Patients in group B presented additionally significantly higher IL-6 levels compared to controls (p<0.01). Occludin expression was significantly decreased in groups A and B compared to group C (p<0.0001 and p<0.001, respectively). Interestingly, in CKD patients (groups A and B) a gradient of occludin expression along the length of the villi, from crypt to tip was recorded with greater loss of its expression at villous tip. Claudin-1 expression was significantly decreased in crypts in groups A and B compared to group C (p<0.0001 and p<0.01 respectively). Endotoxin concentrations were inversely correlated with intestinal occludin (p<0.0001) and claudin-1 (p<0.01) expression and positively correlated with serum IL-6 (p<0.05) and IL-8 (p<0.001) levels. Subgroup analysis for patients with IgA nephropathy showed similar histological findings for occludin and claudin-1 expression as well as for serum endotoxin levels. Conclusion Decreased enterocytes’ occludin and claudin-1 expression, might represent an important mechanism of intestinal barrier disruption and increased gut permeability in patients with CKD.