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Abstract: TH-PO305

Renal Adaptation to Increased Fecal Potassium Excretion by Sodium Zirconium Cyclosilicate

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic

Authors

  • Marmol Mosquera, Fernando Anibal, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Badaruddin, Mohammed Qursheed Muzzammil, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Baig, Athar, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Tahaei, Seyedmohammadebrahim, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Bamberg, Krister, Translational Science and Experimental Medicine, Early Cardiovascular, Renal and Metabolsim (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Potassium (K+) binders, like sodium zirconium cyclosilicate (SZC) which is very selective for K+, are increasingly used for treatment of hyperkalemia. While the efficacy of SZC is clinically proven regardless of underlying condition associated with hyperkalemia, the renal response has not been well studied. We hypothesized that any enhancement on fecal K+ excretion should elicit a renal response characterized by a switch from the normal secretory mode to a reabsorptive mode as a mechanism to conserve K+ and prevent total K+ depletion. This hypothesis was studied in normal mice and in mice with CKD caused by 5/6 nephrectomy to mimic the clinical setting where K+ binders are typically used.

Methods

Mice (CD-1 background) on a regular diet for 2 days were switched to a diet containing SZC for the following 3 days and placed in metabolic cages designed to collect urine and feces separately but simultaneously over a period of 6 hours to be able to assess fecal and urine K+ excretion.

Results

The SZC diet resulted in an increase in fecal potassium (K+) excretion in normal mice (from 15 ±3 to 68 ±9 umol/6hrs p<0.0003) and a similar increase in mice with CKD (from 25 ±2.6 to 87 ±7.1 umol/6hrs p=0.003). Urine potassium K+ excretion, in normal mice decreased markedly (from 89 ±6.9 to 52 ±3.7 umol/6hrs p<0.0003), whereas in CKD mice urine K+ excretion also decreased but to a lesser extent (from 81 ±5.2 to 60 ± 5.1 umol/6hrs p<0.0086). As a result, the increase of total potassium excretion (Fecal + Urine) during the SZC containing diet was statistically significant in CKD (from 106 ±8.5 to 147 ±13 umol/6hrs p=0.012) but not in normal mice (from 104 ±7.1 to 120 ±10.9 umol/6hrs p=0.1428) (fig.1)

Conclusion

In a mouse model of CKD caused by kidney ablation there is a compensatory decrease in renal K+ excretion during fecal K+ loss caused by SZC which is less pronounced than in normal mice owing to less effective K+ renal reabsorption.

Funding

  • Commercial Support –