Fecal Ammonium in mice with CKD: gastrointestinal sequestration by SZC.

Urinary Ammonium (NH) excretion is decreased in CKD but very little is known about fecal NHexcretion. Sodium Zirconium Cyclosilicate (SZC) is a cation-exchanger that selectively captures K in the gastrointestinal tract. We investigated if SZC can sequester NH in vivo and evaluated the effect of SZC on fecal NH 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 (4g/Kg) and followed for 7 days. Feces NH was measured before and after addition of 50 mEq KCl/L to release NH from SZC. NH sequestered in SZC in the gastrointestinal tract was estimated from the delta fecal NHobserved when KCl was added to liberate the sequestered NH. In mice with CKD fecal NH excretion was higher than in normal mice and also higher than urine NH excretion measured concurrently. Using data pooled from the SZC diet, the delta NH was 6.5 ± 0.6 as compared to 0.6 ± 0.6 µmol/g on the normal diet p<0.0001. Fecal NH excretion in CKD is increased and about 6-fold higher than urine NH excretion revealing an important route of elimination of NH present in the GI tract. SZC administration sequesters a substantial portion of NH in the GI tract suggesting that the binding of NH offers therapeutic potential beyond its known primary action as a specific K binder.