ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO583

CKD Disrupts the Intestinal Mucosal Barrier by Altering Occludin Expression

Session Information

  • Pathology and Lab Medicine
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Georgopoulou, Georgia Andriana, Division of Nephrology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
  • Bosgana, Pinelopi, Department of Pathology, University of Patras Medical School, Patra, Greece
  • Papasotiriou, Marios, Division of Nephrology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
  • de Lastic, Anne-Lise, Division of Hematology, Department of Internal Medicine, University of Patras Medical School, Patra, Greece
  • Papachristou, Evangelos, Division of Nephrology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
  • Goumenos, Dimitrios S., Division of Nephrology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
  • Zolota, Vasiliki, Department of Pathology, University of Patras Medical School, Patra, Greece
  • Assimakopoulos, Stelios F., Division of Infectious Diseases, Department of Internal Medicine, University of Patras Medical School, Patra, Greece
Background

The gut barrier function is compromised in chronic kidney disease (CKD) resulting in increased gut permeability. However, little is known on the potential implicated mechanism(s). This study was undertaken to investigate intestinal occludin expression (a molecular component of epithelial tight junctions) in patients with CKD of various stages.

Methods

Thirty-three patients with CKD stage I-IV (n=17) or end-stage kidney disease (ESKD) (n=16) and 11 healthy controls were subjected to duodenal biopsy. Specimens were examined histologically and the villous heigh/crypt depth ratio and apoptotic body count (by morphology) in the cryptal epithelium was recorded. The expression of occludin in the intestinal epithelium was evaluated by immunohistochemistry. Circulating endotoxin concentration was evaluated by enzyme-linked immunosorbent assay.

Results

Patients with CKD stage I-IV or ESKD presented significantly higher serum endotoxin concentrations as compared to controls (P<0.001, respectively). There was an increase of cryptal apoptotic body count in CKD and ESKD patients (P<0.001 vs. controls) and a trend towards decreased villous heigh/crypt depth ratio. Occludin expression was significantly decreased in CKD and ESKD patients as compared to controls (P<0.001) (Table 1). Interestingly, a gradient of occludin expression from the crypt to the tip of the villi was recorded; occludin expression was retained in crypts, it was reduced in the middle part of the villi, while greater loss of its expression was observed at the upper part.

Conclusion

Decreased intestinal occludin expression, observed mainly at the upper third of the villi and increased crypt epithelial apoptosis might represent important mechanisms for intestinal barrier dysfunction and hyperpermeability in patients with CKD or ESKD.

TABLE 1: Occludin immunohistochemical expression: (%) of positive enterocytes (mean±SD)
 CKD stage I to IV (n=17)ESKD
(n=16)
CKD (total)
(n=33)
Healthy controls (n=11)
Total occludin (%) of enterocytes75,3±6,2*77,2±9,6*76,3±8*90,9±9,4
Tip of villi (%)44,7±25*50,6±29*47,7±27*86,4±13,6
Middle of villi (%)84,7±6,2*85±7,9*84,9±7*97,3±4,7
Crypt (%)97±5,993,3±10,995,1±8,999±3
*p<0.001 vs. controls