PUK15 a Managed Care Cost-Offset Model for Ferric Citrate, an Experimental Phosphate Binder That Can Reduce the Use of Erythropoiesis-Stimulating Agents and Intravenous Iron in Hemodialysis Patients with Hyperphosphatemia

Abstract Background and Aims Gut microbiome alteration increases uremic toxin levels inducing chronic inflammation and leading morbidity and mortality in patients with chronic kidney disease. Phosphate-binding agents may potentially change the composition of the gut microbiota. However, the limited clinical study investigates the microbiome difference between iron-containing and calcium-containing phosphate binders. The aim of this study was to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. Method The stool microbiota was investigated in hemodialysis patients with ferric citrate used (n=8) and calcium carbonate used (n=46) by 16S rRNA next-generation gene sequencing profiling. The altered microbiota between two different phosphate binders was analyzed. Differences in the microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Results Hemodialysis patients with calcium carbonate used revealed significantly reduced microbial species diversity (Shannon index and Simpson index) and increased microbial dysbiosis index compared with ferric citrate users. Compared to patients taking calcium carbonate, a distinct microbial community structure in patients taking ferric citrate, with an increased abundance of Bacteroidetes phylum and decreased abundance of phylum Firmicutes. In comparison between two phosphate binder users, members of the order Lactobacillales were prominent in calcium carbonate therapy, including family Streptococcaceae and genus Streptococcus. In contrast, taxa of the genus Ruminococcaceae, Flavonifractor, and Cronobacter were enriched in ferric citrate phosphate binder users. Conclusion The fecal microbiota was richer and more diverse in the ferric citrate group than in the calcium carbonate group. Hemodialysis patients with ferric citrate used were associated with differences in the gut microbiome composition compared to calcium carbonate users.

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Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease

Microorganisms ◽

10.3390/microorganisms8122040 ◽

2020 ◽

Vol 8 (12) ◽

pp. 2040

Author(s):

Ping-Hsun Wu ◽

Po-Yu Liu ◽

Yi-Wen Chiu ◽

Wei-Chun Hung ◽

Yi-Ting Lin ◽

...

Keyword(s):

Calcium Carbonate ◽

Kidney Disease ◽

Gut Microbiome ◽

Phosphate Binder ◽

Hemodialysis Patients ◽

Ferric Citrate ◽

Phosphate Binders ◽

Rrna Gene ◽

Phosphate Binding ◽

Linear Discriminant

Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.

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