To the best of our knowledge, this retrospective study is the first to investigate the clinical significance of La deposition in the gastric mucosa (as in Study 1), and the association between endoscopic features and histologic findings (as in Study 2).
In Study 1, the most important finding was that there was no significant difference between patients with and without La deposition in the gastric mucosa in terms of blood test findings. In addition, there was no significant difference between the patients taking LaC and those not taking LaC. These results show that gastric La deposition may not cause clinical problems and LaC might be a safe treatment for hyperphosphatasemia in patients with chronic kidney disease on hemodialysis even if La deposits occur in the gastric mucosa. It was revealed that the total dose of LaC was significantly correlated with La deposition in the gastric mucosa. Although our result was similar to our previous report, this study differs in that the daily dose of LaC was not related to La deposition [3]. We had predicted that the daily dose might not significantly affect La deposition when the period of LaC administration was longer. In addition, concomitant drugs (PPIs, H2RAs, NSAIDs, and gastric mucoprotective drugs) did not affect the deposition of La in the gastric mucosa. Although Shitomi et al. reported that the histological finding of Helicobacter pylori infection might decrease the deposition of La [5], Ban et al. reported that the lesions associated with Helicobacter pylori infection, such as intestinal metaplasia, regenerative changes, and foveolar hyperplasia were more frequently observed in mucosa with large quantities of La deposits [6, 7]. Given that our present study also showed that the range of atrophic changes in the gastric mucosa was not associated with La deposition, Helicobacter pylori infection may not be associated with the deposition of La in the gastric mucosa.
Study 2 revealed that the gastric endoscopic findings of La deposition reflected the infiltrated histiocytes, not the La deposition itself. The appearance of histiocytes must depend on the amount of La deposition, which acts as foreign matter to which histiocytes react. We suggest that the whitish lesions of La deposition reflect the existence of macrophages, similar to gastric xanthoma. La deposition was also detected from non-whitish normal mucosa. In summary, the specific features of La deposition reflect the body’s normal reaction to foreign bodies. However, the reason the histiocytic infiltration was divided clearly into two groups (less than 30% and more than 80%) is uncertain.
Although gastric La deposition may not cause clinical problems and LaC might be safe for hyperphosphatasemia in patients with chronic kidney disease on hemodialysis, it has been reported that several side effects of gastrointestinal symptoms have been associated with LaC, such as nausea, vomiting, and constipation [9]. These symptoms might be caused by gastrointestinal motility dysfunction. As it has been reported that functional dyspepsia is caused, in part, by Helicobacter pylori infection [10], the gastrointestinal symptoms in hemodialysis patients taking LaC might be caused by La deposition even if there is no organic lesion. Although it has been reported in a pharmacological safety study of LaC that it has no significant effects on gastric emptying and intestinal transit time at high doses [11, 12], an association between La deposition in the gastric mucosa has been loosely associated with gastric peristalsis. Because the present study did not investigate the relationship between the gastrointestinal symptoms and motility function, we should plan the next study to investigate gastric motility function in hemodialysis patients undergoing LaC treatment.
The present study had some limitations. First, the sample size was small, as this was a single-center retrospective study. In addition, there was some missing blood test data. Second, there may have been patients with gastric La deposition in the La-negative group in Study 1 because Study 2 revealed that La deposition was sometimes detected on biopsy specimens from normal gastric mucosa. Third, although La is often deposited at the duodenal mucosa [8], we did not evaluate duodenal La deposition in the present study because of the low number of subjects or biopsy specimens. There might be a relationship between duodenal La deposition and some background factors.
In conclusion, we demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by any background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies.