NCR-19-2039- Ammonium excretion in ZS-9 treated mice with CKD

Hyperkalemia is a common electrolyte disorder that often occurs in patients with impaired renal function The risk of developing hyperkalemia is increased by the use of drugs that alter K+ balance such as K+ sparing diuretics and blockers of the renin-angiotensin-aldosterone system (RAAS) (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers, spironolactone). Although hyperkalemia is generally asymptomatic, it may lead to life-threatening arrhythmias and is an independent risk factor for cardiovascular mortality. Chronic hyperkalemia is often associated with metabolic acidosis . Currently, both disorders are treated independently which means an increase in pill burden for patients with CKD who are the ones that most frequently experience both problems. It is reasonable to expect that lowering plasma K may improve metabolic acidosis particularly when the hyperkalemia is severe. In addition, ZS-9 may have an important additional effect by increasing fecal ammonium excretion owing to its affinity for not only K+ but also NH4+ binding in the gastrointestinal tract. It is anticipated that in mice with normal kidney function ZS-9 will increase K+ and ammonium fecal excretion. In mice with CKD ZS-9 will also increase both K+ and ammonium fecal excretion. In addition to this changes in urinary and fecal excretions it is expected that plasma HCO3- will increase significantly. All the expected changes will be accentuated in animals treated with a high K diet to increase plasma K levels.