Esomeprazole Induces a Transepithelial Gastroesophageal Mucosal Leak in GERD Patients

Abstract

Proton pump inhibitors are well documented to alleviate inflammation and erosions associated with reflux disease. We hypothesized that a standard 8-week course of esomeprazole therapy would reduce the elevated transepithelial, paracellular sucrose leak that we have observed in esophagitis patients. Sucrose can cross the upper gastrointestinal mucosal barrier as a disaccharide only by paracellular leaks. 17 study subjects presenting to their primary care physician with symptoms of GERD were placed on an 8 week course of esomeprazole (40 mg/day in the morning). Subjects either had no prior exposure to proton pump inhibitors or H-2 blockers, or had not taken either class of medication for at least 30 days. All subjects reported alleviation of reflux symptoms at 4 and 8 week compliance checks. Immediately prior to beginning esomeprazole therapy, all subjects performed a sucrose permeability test consisting of drinking a solution of 100 gms of sucrose in 200 cc of water followed by an overnight urine collection. Sucrose leaking across the upper GI tract was accounted for by its appearance in the overnight urine, whose sucrose concentration was assayed by enzymatic methods. A second sucrose leak test was performed at the end of the 8 week course of esomeprazole. The initial hypothesis was for a decreased sucrose leak due to esomeprazole-mediated healing of gastroesophageal inflammation. The reverse was observed in the majority of patients. Two outliers were removed from the group of 17 based upon an initial sucrose leak nearly 10-fold greater than the average of the remaining patients and a subject history that indicated usage of NSAIDs and/or steroids at the time of the initial sucrose test. Of the remaining 15 subjects, the mean age was 51 with a range of 24 to 85 years. 7 were male; 8 were female. 7 were Caucasian, 7 were Black, and 1 was Asian. 7 had a BMI over 30; 8 were under 30. The mean sucrose leak before beginning esomeprazole therapy was 119 mg ± 25 mg (SEM) vs a mean sucrose leak of 366 mg ± 85 mg. (P < 0.02, paired Student's t) immediately upon finishing esomeprazole therapy (mean difference of 247.1 ± (90.6) mg). Minimum, median and maximum sucrose leak values were 18, 97 and 362 mg respectively, for the initial sucrose test, and 31, 243 and 1297 mg for the final sucrose test. The median difference score was 137.6 (P < 0.025, Wilcoxon signed rank test). The difference between initial and final sucrose leak was observed to be greater for Caucasians, for males, for ages greater than 50, and for BMI less than 30. Supported in part by research grants from Astra Zeneca, the Oncologic Fndn. of Buffalo and the PA Dept. of Health.