New Potassium Binders for the Treatment of Hyperkalemia
Hyperkalemia is a clinical problem with potential mechanisms ranging from increased cellular potassium release (eg, pseudohyperkalemia, metabolic acidosis) to reduced potassium excretion (eg, reduced responsiveness to aldosterone, reduced aldosterone secretion, reduced distal sodium, and water delivery).1,2 Patients with chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m2, are at increased risk of hyperkalemia, resulting from ≥1 of these mechanisms.3 Renin–angiotensin–aldosterone system inhibitors (RAASis) are recommended by guidelines for lowering blood pressure, slowing CKD progression in patients with CKD,4,5 and reducing cardiovascular mortality and heart failure hospitalizations in patients with heart failure and a reduced ejection fraction,6,7 but these drugs compound the hyperkalemia risk.1,8–10 The risk is magnified when the drugs are used in combination (eg, aliskiren in combination with ACE inhibitors or angiotensin receptor blockers;8,11 mineralocorticoid receptor antagonists in combination with ACE inhibitors or angiotensin receptor blockers). Moreover, the risk for hyperkalemia is magnified in diseases, such as diabetes mellitus and heart failure.4,5,12,13 The occurrence or fear of inducing hyperkalemia has led to premature discontinuation, suboptimal dosing, and often failure to use an RAASi, thereby exposing patients to increased cardiovascular risk.

Current treatment approaches for chronic hyperkalemia are limited. Options for the management of hyperkalemia include discontinuation or reduced doses of RAASi, administration of loop diuretics, dietary potassium restriction, or sodium polystyrene sulfonate.14 None of these approaches are optimal because they require withholding life-saving or kidney preserving therapy (ie, RAASi), have a low rate of patient adherence (eg, dietary restriction), or have an unfavorable adverse effect profile and low tolerability (ie, sodium polystyrene sulfonate).15

New agents to treat hyperkalemia are in the late …