Fecal ammonium in mice with CKD: gastrointestinal sequestration by sodium zirconium cyclosilicate

Fernando Marmol, Mohammed Badaruddin, Athar Baig, Minghao Ye, Jan Wysocki, Ebrahim Tahaei, Paul Welling, Krister Bamberg, Daniel Batlle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Urinary NH4+ excretion is decreased in chronic kidney disease (CKD), but very little is known about fecal NH4+ excretion. Sodium zirconium cyclosilicate (SZC) is a cation exchanger that selectively captures K+ in the gastrointestinal tract. We investigated if SZC can sequester NH4+ in vivo and evaluated the effect of SZC on fecal NH4+ in a mouse model of CKD. Mice with CKD induced by 5/6 kidney ablation were fed either a regular diet or a diet containing SZC (4 g/kg) and followed for 7 days. Fecal NH4+ was measured before and after the addition of 50 meq KCl/L to release NH4+ from SZC. NH4+ sequestered in SZC in the gastrointestinal (GI) tract was estimated from the change in fecal NH4+ observed when KCl was added to liberate the sequestered NH4+. In mice with CKD, fecal NH4+ excretion was higher than in normal mice and also higher than urine NH4+ excretion measured concurrently. Using data pooled from the SZC diet, the change in NH4+ was 6.5±0.6 compared with 0.6±0.6 lmol/g on the normal diet (P < 0.0001). In conclusion, fecal NH4+ excretion in CKD is increased and about sixfold higher than urine NH4+ excretion, revealing an important route of elimination of NH4+ present in the GI tract. SZC administration sequesters a substantial portion of NH4+ in the GI tract, suggesting that the binding of NH4+ offers therapeutic potential beyond its known primary action as a specific K+ binder.

Original languageEnglish (US)
Pages (from-to)F464-F471
JournalAmerican Journal of Physiology - Renal Physiology
Volume324
Issue number5
DOIs
StatePublished - May 2023

Keywords

  • acid-base disorder
  • ammonium
  • chronic kidney disease
  • gut

ASJC Scopus subject areas

  • Urology
  • Physiology

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