Effect of sucroferric oxyhydroxide on gastrointestinal microbiome and uremic toxins in patients with chronic kidney disease undergoing hemodialysis

Clin Exp Nephrol. 2020 Aug;24(8):725-733. doi: 10.1007/s10157-020-01892-x. Epub 2020 Apr 13.

Abstract

Background: In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis.

Methods: In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis.

Results: Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl, P = 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl, P = 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species.

Conclusion: Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.

Keywords: Chronic kidney disease; Gastrointestinal microbiome; Indoxyl sulfate; Serum uremic toxin; Sucroferric oxyhydroxide; p-Cresyl sulfate.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cresols / blood
  • Drug Combinations
  • Dysbiosis / drug therapy*
  • Dysbiosis / etiology
  • Feces / microbiology
  • Ferric Compounds / pharmacology
  • Ferric Compounds / therapeutic use*
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Indican / blood
  • Middle Aged
  • Renal Dialysis
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / microbiology*
  • Renal Insufficiency, Chronic / therapy
  • Sucrose / pharmacology
  • Sucrose / therapeutic use*
  • Sulfuric Acid Esters / blood

Substances

  • Cresols
  • Drug Combinations
  • Ferric Compounds
  • Sulfuric Acid Esters
  • sucroferric oxyhydroxide
  • 4-cresol sulfate
  • Sucrose
  • Indican