Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

Background: Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility. Methods: Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins. Results: The CKD rats showed marked azoteReceived: May 11, 2013 Accepted: June 17, 2013 Published online: July 23, 2013 Nephrology American Journal of N.D. Vaziri, MD, MACP Division of Nephrology and Hypertension, Suite 400, City Tower University of California, Irvine Medical Center 101 The City Drive, Orange, CA 92868 (USA) E-Mail ndvaziri @ uci.edu © 2013 S. Karger AG, Basel 0250–8095/13/0382–0099$38.00/0