The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease
Open accessAbstract
Background: Chronic kidney disease (CKD) impairs intestinal barrier function which leads to endotoxemia and systemic inflammation. We have found depletion of intestinal epithelial tight junction (TJ) proteins in animals with CKD. We further showed that addition of end-stage renal disease patients’ plasma to the culture medium provokes a marked drop in transepithelial electrical resistance (TER) and depletion of TJ proteins in cultured human enterocytes. These effects were less severe with post- than with prehemodialysis plasma, suggesting a role of dialyzable agent(s). This study tested the hypothesis that intestinal barrier dysfunction in uremia may be due to diffusion of urea into the gut and its conversion to ammonia by microbial urease. Methods: Human enterocytes (T84 cells) were seeded on Transwell plates and utilized when TER exceeded 1,000 mΩ·cm 2 to ensure full polarization and TJ formation. Confluent cells were then incubated for 24 h in media containing 0, 42 or 74 mg/dl urea or urea plus urease to simulate presence of microbial flora. Results: At clinically relevant concentrations, urea caused a concentration-dependent fall in TER and the key TJ proteins claudin-1, occludin and zonula occludens 1. The effects of urea were dramatically amplified by urease causing cell detachment, dissipation of TER, and massive loss of TJ proteins. Conclusions: Uremia-induced disruption of intestinal TJ and barrier function is, in part, mediated by urea which is generally considered to be a nontoxic retained metabolite. These findings reveal a novel mechanism for a salutary effect of urea-lowering strategies, e.g. low-protein diet and longer and more frequent dialysis regimens in advanced CKD.
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Chronic kidney disease alters intestinal microbial flora
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Self-citationResponses of lymphocytes to anisotonic media: volume-regulating behavior
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Self-citationEndotoxemia is Related to Systemic Inflammation and Atherosclerosis in Peritoneal Dialysis Patients
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The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753
Nutritional Management of Chronic Kidney Disease
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Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target
Ramezani, A., Massy, Z. A., Meijers, B., Evenepoel, P., Vanholder, R., & Raj, D. S. (2016) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2015.09.027 · Cited by 394
A novel SCFA receptor, the microbiota, and blood pressure regulation
Pluznick, J. (2014) · Gut Microbes · doi:10.4161/gmic.27492 · Cited by 374
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Metadata
- Authors
- Vaziri, N. D., Yuan, J., & Norris, K.
- Venue
- American Journal of Nephrology
- Publisher
- S. Karger AG
- Published
- 2012-12-19
- Volume
- 37
- Issue
- 1
- Pages
- 1-6
- ISSN
- 0250-8095 (ISSN-L)
- 1421-9670
- OpenAlex
- W1987241524
- Cited by
- 381
- References
- 19
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- green
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