Correlation of lanthanum dosage with lanthanum deposition in the gastroduodenal mucosa of dialysis patients

Abstract

Lanthanum (La) deposition has been observed in gastrointestinal mucosa of dialysis patients treated with La carbonate to treat hyperphosphatemia in the 6 years since its authorization in Japan. We investigated gastrointestinal biopsies from 112 dialysis patients, and found 15 cases of histiocytic aggregation with crystalloids and one case of duodenitis with histiocyte aggregation without crystalloids in the 30 patients treated with La carbonate. No histiocytic lesions were observed in the 82 patients without La carbonate administration. So far in total 70 cases of La deposition in the alimentary tract have been reported, including our 16 cases. Neither clinical nor histological findings other than histiocytic aggregation were specific in the patients with La deposition. We also compared the groups with and without La deposition, revealing that the daily and total doses of La carbonate showed statistically significant correlations with La deposition. However the causality with their histologic features, e.g. intestinal metaplasia and degree of inflammation, were inconclusive between the two groups. Although no critical symptoms have been reported, it is necessary to accumulate more cases to clarify the mechanism of La deposition, because dialysis patients must take phosphate buffers for a long period.

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

“…At the present time, which has seen rapid strides in the development of omics analysis technologies, such as genome analysis, it is expected that data‐driven studies based on analysis of clinical samples will help clarify the molecular mechanisms responsible for the occurrence, progression and treatment responsiveness of diseases, thereby leading to the development of new biomarkers for diagnosis and identification of drug discovery targets . In particular, analysis of pathological tissue samples collected from the exact site of a disease, such as cancer, will be indispensable for the realization of genomic medicine …”

“…3 In particular, analysis of pathological tissue samples collected from the exact site of a disease, such as cancer, will be indispensable for the realization of genomic medicine. [4][5][6][7][8][9][10][11][12] Besides detailed and accurate clinicopathological information about pathological tissue samples, the quality of the tissue samples itself holds the key to the success of such data-driven studies. 13,14 Appropriate collection and storage of pathological tissue samples enables reliable and high-quality analyses that can contribute to prevention and treatment of diseases.…”

Utility of Scanning Electron Microscopy Elemental Analysis Using the ‘NanoSuit’ Correlative Light and Electron Microscopy Method in the Diagnosis of Lanthanum Phosphate Deposition in the Esophagogastroduodenal Mucosa

“…To explore whether SEM observation using the NanoSuit-CLEM method is useful for the diagnosis of lanthanum phosphate deposition in the gastrointestinal tract, we first performed SEM observation in six cases (cases 1-6) having a pathological record of brown pigment deposition, which were suspected as lanthanum phosphate deposition, in the H&E slides, either or both of stomach and duodenum (Figure 2a; representative images showing deposition exhibiting granular, needle-shaped, or amorphous structure), known as target organs of lanthanum phosphate deposition [8,12]. The same area was observed with the aid of the NanoSuit-CLEM method.…”

“…Lanthanum carbonate binds with ingested phosphate to form insoluble complexes in the digestive tract, which are excreted with the feces [2]. However, recent reports have reported that small amounts of lanthanum phosphate are deposited in the stomach and duodenum in patients treated with lanthanum carbonate [3][4][5][6][7][8][9][10][11][12][13][14][15]. The lanthanum phosphate deposition is frequently observed especially in the stomach [6,14], and is suggested to be associated with some pathological conditions such as intestinal metaplasia and foveolar hyperplasia [5,7,8,14].…”

“…As various pathological lesions, including malignant neoplasia, can occur in the stomach and duodenum, differential diagnosis of lanthanum phosphate deposition from these pathological lesions is important. In light microscopic observation with hematoxylin and eosin (H&E) staining, the deposits appear as a brown granular, needle-shaped, or amorphous substance within and outside the histiocytes [9,12]. Sometimes their colors are described as eosinophilic, grey, or purple [3,7,9,13].…”