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Abstract: TH-PO933

Calcium- and Iron-Based Phosphate Binders Impact the Gut Microbiome in Rats with CKD

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Biruete, Annabel, Purdue University, West Lafayette, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • De loor, Henriette, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Evenepoel, Pieter, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Swanson, Kelly, University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Limited studies suggest that phosphate binders may impact the gut microbiome. Our objective was to examine the effects of a calcium-based binder and an iron-based binder on the cecal microbiota and gut-derived uremic toxins in a rat model of progressive CKD.

Methods

Rats with normal kidney function (NL) were compared to rats with CKD (Cy/+ male rats): 1) control (CKD), 2) 2% ferric citrate (CKD + FC), 3) 2% calcium gluconate in water (CKD +Ca). Rats consumed the treatments for 10 weeks (18 to 28 weeks of age; mild to moderate/advanced CKD, respectively). The V4 region of the 16S rRNA gene was sequenced from cecal digesta and analyzed using QIIME2. Serum gut-derived uremic toxins were quantified using ultra-performance liquid chromatography-tandem mass spectrometry.

Results

Richness of the microbiota (alpha-diversity) was similar between groups, but overall microbial composition (beta-diversity) was different from each other. At the phylum-level, all CKD rats had lower relative abundance of Firmicutes, and CKD+Ca had higher Bacteroidetes. At the genus-level, CKD+FC had a higher relative abundance of Akkermansia, unclassified Desulfovibrionaceae, and Clostridium, and a lower relative abundance of Allobaculum, Bifidobacterium, and Lactobacillus. CKD+Ca had higher relative abundance of unclassified Lachnospiraceae and Blautia. Indoxyl sulfate and p-cresyl sulfate were elevated in CKD but were not affected by phosphate binders. However, phenyl sulfate and phenyl glucuronide were lower in CKD+Ca.

Conclusion

Calcium- and iron-based phosphate binders altered the gut microbiota, but only the calcium-based binder impacted phenyl-derived uremic toxins.

Funding

  • NIDDK Support – Keryx pharmaceuticals for parent study.