A Combined Deposition of Lanthanum and β2-Microglobulin-Related Amyloid in the Gastroduodenal Mucosa of Hemodialysis-Dependent Patients: An Immunohistochemical, Electron Microscopic, and Energy Dispersive X-Ray Spectrometric Analysis

Abstract

Lanthanum carbonate (LC) is a new type of phosphate adsorbent used to treat patients with hyperphosphatemia caused by chronic kidney diseases. Recent studies have pointed out that lanthanum deposition can be found in the cytoplasm of histiocytes in the gastroduodenal mucosa of these patients. On the other hand, it is well known that patients on long-term hemodialysis can develop deposition of β2-microglobulin-related amyloid (Aβ2M) mainly around joints. However, involvement of the gastrointestinal tract by hemodialysis-associated amyloidosis has been thought to be rare, and therefore only Aβ2M, if any, has been reported to accumulate in the vascular walls of the submucosa and muscularis propria. Thus, in contrast to AA amyloid, biopsy from gastrointestinal mucosa has long been considered to have little significance in detecting amyloid. We present unusual histologic findings on biopsy specimens taken from the gastroduodenal mucosa of 7 hemodialysis-dependent patients taking LC for more than a year. These findings were due to a combined deposition of lanthanum and β2-microglobulin-related amyloid in the cytoplasm of histiocytes. The deposition of amyloid was confirmed by conventional histochemistry, immunohistochemistry, and transmission electron microscopy, and that of lanthanum by transmission electron microscopy and scanning electron microscopy/energy dispersive X-ray spectrometry. This is the first report of such a peculiar combined deposition of lanthanum and amyloid in the gastroduodenal mucosa of hemodialysis patients. Although the exact mechanism of combination and pathogenesis is unclear, we believe that histologic examination of the gastrointestinal mucosa should be considered in the careful follow-up and observation of hemodialysis patients taking LC.