Sodium zirconium cyclosilicate (ZS-9) for the treatment of hyperkalemia

Hyperkalemia is a common, sometimes fatal electrolyte abnormality seen in patients with heart failure (HF) or kidney disease. Acute treatments that cause the intracellular translocation of potassium can be effective in the short-term but they simply buy time until definitive removal by dialysis or binding agents (e.g., sodium polystyrene sulfonate) can occur. In contrast, treatment for chronic hyperkalemia, which often occurs in the setting of HF treated with renin-angiotensin-aldosterone inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA), is limited and has questionable efficacy.

Sodium zirconium cyclosilicate (ZS-9), a novel, non-absorbed, potassium-selective cation exchanger, has demonstrated activity in acutely lowering and maintaining normal potassium levels. When used chronically, maintenance of normal serum potassium has been demonstrated for up to 1 month. Although higher doses of ZS-9 have been associated with modest increases in the rates of edema and hypokalemia, the overall adverse event rate is similar to placebo.

The efficacy of ZS9 has been shown in patients with chronic hyperkalemia, offering promise for conditions such as HF, where optimized therapy with RAASi and MRA is often limited by a concomitant, drug-induced increase in potassium. Further, in acute hyperkalemia it has potential to become an important option by rapidly lowering potassium levels, thus delaying or potentially averting the need for emergent dialysis. While further randomized trials demonstrating improved clinical outcomes are required for both these indications, initial data suggests a promising role for this agent in the management of both acute and chronic hyperkalemia.