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

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.