Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Endotoxin and Cytokines Measurements
2.3. Histopathological Evaluation and Immunohistochemistry
2.4. Statistical Analysis
3. Results
3.1. Patients’ Characteristics
3.2. Endotoxin Concentrations
3.3. Cytokine Levels
3.4. Intestinal Histopathology
3.5. Immunohistochemistry for TJ Proteins and Intraepithelial CD3(+) T-Lymphocytes
3.6. Correlations
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Control (n = 11) | Stage I–IV CKD (n = 17) | ESKD (n = 16) |
---|---|---|---|
Age (years) | 49.7 ± 18.5 | 58.5 ± 12.5 | 57.7 ± 13.4 |
Sex (males/females) | 5/7 | 10/7 | 11/5 |
Urea (mL/dL) | 30 ± 3.9 | 63.8 ± 39 * | 123.5 ± 39 ** |
Creatinine (mL/dL) | 0.75 ± 0.09 | 0.75 ± 0.4 * | 5.9 ± 2.3 ** |
eGFR (mL/min/1.73 m2) | 106.6 ± 19 | 56.5 ± 23.7 ** | <15 |
Causes of CKD | |||
Diabetic Nephropathy | N/A | 2 | 5 |
Hypertensive Nephropathy | N/A | 0 | 4 |
Glomerulonephritis | N/A | 13 | 2 |
Interstitial Nephritis | N/A | 0 | 2 |
Other | N/A | 2 | 1 |
Unknown | N/A | 0 | 2 |
CKD Classification | |||
Stage I (eGFR ≥ 90) | N/A | 3 | 0 |
Stage II (eGFR = 60–89) | N/A | 2 | 0 |
Stage IIIA (eGFR = 45–59) | N/A | 7 | 0 |
Stage IIIB (eGFR = 30–44) | N/A | 4 | 0 |
Stage IV (eGFR = 15–29) | N/A | 1 | 0 |
Stage V (eGFR < 15) | N/A | 0 | 16 |
Renal replacement method | |||
Hemodialysis | 10 | ||
Peritoneal dialysis | 6 |
Cytokine | Controls (n = 11) | Stage I–IV CKD (n = 17) | ESKD (n = 16) |
---|---|---|---|
IL-1β (pg/mL) | 0 (0–0.53) | 0 (0–0) | 0 (0–0) |
IL-6 (pg/mL) | 0.83 (0.57–1.85) | 10.36 (8.35–19.36) ** | 19.33 (0.58–59.43) ** |
IL-8 (pg/mL) | 3.42 (2.5–6.94) | 41 (14.87–102) * | 126.3 (33.9–475) *** |
IL-10 (pg/mL) | 0.28 (0.18–0.37) | 2.8 (0.96–4.23) *** | 1.85 (0.64–3.1) ** |
TNF-a (pg/mL) | 0.41 (0–1.3) | 0 (0–4.7) | 0 (0–4) |
Histopathological Features | Controls (n = 11) | Stage I–IV CKD (n = 17) | ESKD (n = 16) |
---|---|---|---|
Apoptotic body count | 10 (5–10) | 5 (5–10) | 7.5 (5–10) |
Villous length (mm) | 0.42 ± 0.03 | 0.40 ± 0.13 | 0.34 ± 0.1 |
Intraepithelial CD3+ lymphocytes/100 intestinal epithelial cells | 15 (15–20) | 5 (5–7.5) | 10 (5–17.5) |
Occludin Expression | Controls (n = 11) | CKD Stage I–IV (n = 17) | ESKD (n = 16) |
---|---|---|---|
Part of the villi | |||
Τip | 91.8 ± 7.5 | 44.7 ± 25 ** | 53.7 ± 29 ** |
Μiddle | 97.3 ± 4.7 | 84.7 ± 6.2 ** | 86.3 ± 7.2 * |
Crypt | 99 ± 3 | 97 ± 5.9 | 93.1 ± 11.3 |
Total expression | 93.6 ± 5 | 75.3 ± 6.2 ** | 77.5 ± 10 ** |
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Georgopoulou, G.-A.; Papasotiriou, M.; Bosgana, P.; de Lastic, A.-L.; Koufou, E.-E.; Papachristou, E.; Goumenos, D.S.; Davlouros, P.; Kourea, E.; Zolota, V.; et al. Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability. Biomedicines 2024, 12, 368. https://doi.org/10.3390/biomedicines12020368
Georgopoulou G-A, Papasotiriou M, Bosgana P, de Lastic A-L, Koufou E-E, Papachristou E, Goumenos DS, Davlouros P, Kourea E, Zolota V, et al. Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability. Biomedicines. 2024; 12(2):368. https://doi.org/10.3390/biomedicines12020368
Chicago/Turabian StyleGeorgopoulou, Georgia-Andriana, Marios Papasotiriou, Pinelopi Bosgana, Anne-Lise de Lastic, Eleni-Evangelia Koufou, Evangelos Papachristou, Dimitrios S. Goumenos, Periklis Davlouros, Eleni Kourea, Vasiliki Zolota, and et al. 2024. "Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability" Biomedicines 12, no. 2: 368. https://doi.org/10.3390/biomedicines12020368
APA StyleGeorgopoulou, G.-A., Papasotiriou, M., Bosgana, P., de Lastic, A.-L., Koufou, E.-E., Papachristou, E., Goumenos, D. S., Davlouros, P., Kourea, E., Zolota, V., Thomopoulos, K., Mouzaki, A., & Assimakopoulos, S. F. (2024). Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability. Biomedicines, 12(2), 368. https://doi.org/10.3390/biomedicines12020368