#EMConf: New Potassium binding agents for HyperK



What you need to know:

  • Veltassa aka Patiromer
    • Oral potassium binding agent - exchanges K for Ca
    • FDA approved for chronic hyperkalemia
    • No evidence yet supporting use in acute hyperK - more research needed
    • Stays in GI tract and binds K, not systemically absorbed
    • Unlike kayexalate, typically does not cause GI symptoms
  • Lokelma aka sodium zirconium cyclosilicate aka ZS-9:
    • Oral potassium binding agent - highly selective cation exchanger that entraps K in the GI tract in exchange for Na and H+ 
    • Not yet FDA approved
    • Not systemically absorbed, stays in the GI tract, does not expand with water
    • No GI side effects


Study 1: Rafique Z et al. Patiromer for treatment of hyperkalemia in the emergency department: A pilot study. Academic Emergency Medicine. 2019;00:1-7.

  • Single center, randomized, convenience sample pilot study 
  • Objective: assess if there is a difference in serum potassium between the patiromer group compared to standard of care at 6 hours
  • Methods: 30 (15 in each group) adults with hx of dialysis-dependent ESRD in the ED with acute hyperkalemia (K >6.0) were randomized to receive either standard of care alone (not well defined) or standard of care  plus one dose of 25.2 g oral patiromer
  • Results: 6 hour serum K level no significant difference between control (6.32, CI = 6.0-6.63) and study group (5.81, CI = 5.48-6.14). 
  • Limitations: small sample size, significant drop out rate, ill-defined “standard of care” 


Study 2: Kosiborod M et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia. JAMA 2014;312(21):2223–33.

  • Phase III, multicenter, randomized, double-blind, placebo-controlled study of adult patients without hx of ESRD with elevated potassium (K >5.0) in the outpatient setting
  • Objective: Assess if there is a difference in serum potassium levels after 4 weeks of taking sodium zirconium cyclosilicate (ZS-9) at varying doses compared to placebo
  • Methods: All 258 patients received 10 g of ZS-9 three times daily for the initial 48 hour open-label phase. Patients who achieved normokalemia at 48 hours (n = 237) were then randomized to receive 5 g ZS-9 (n = 45), 10 g ZS-9 (n =51), 15 g ZS-9 (n = 56) or placebo (n= 85) daily for 28 days
  • Results: Mean serum K during days 8-29 was significantly reduced in all zirconium cyclosilicate groups vs placebo with numerically lower potassium achieved with higher doses (4.8mEq/L [95%CI, 4.6-4.9], 4.5mEq/L [95%CI, 4.4-4.6], and 4.4mEq/L [95%CI, 4.3-4.5] for 5-g,10-g, and 15-g doses, respectively; 5.1mEq/L [95%CI, 5.0-5.2] for placebo; P<.001 for each zirconium cyclosilicate dose vs placebo comparison
    • During the initial 48 hour open label portion of the study, the ZS-9 group had significantly lower levels of potassium at the 1 hour (−0.2 mEq/L; 95% CI, −0.3 to−0.2; P<.001), 2 hour (−0.4mEq/L(95%CI,−0.5to −0.4; P<.001) and 4 hour (−0.5 mEq/L (95% CI, −0.6 to −0.5; P<.001) marks 
  • Limitations: Excluded ESRD patients; performed in the outpatient setting. Included only patients who responded to the first 48 hours of treatment with ZS-9