Pharmacologic Treatment of Chronic Hyperkalemia in Patients with Chronic Kidney Disease

Hyperkalemia is frequently complicated in patients with advanced chronic kidney disease (CKD) because kidney is the major route of potassium excretion. Urinary potassium excretion is reduced according to the decline in glomerular filtration rate, and the risk of hyperkalemia is increased in patients with high potassium intake, advanced age, diabetes mellitus, congestive heart failure, and medications such as renin-angiotensin-aldosterone system(RAAS) blockades. On the other hand, the benefits of RAAS blockades and a high-potassium diet should be considered in CKD patients. To overcome these contradictory treatment strategies, potassium binders have emerged as new options to enhance fecal potassium excretion. In different regions of the world, four types of potassium binders are preferentially used. Whereas sodium polystyrene sulfonate (SPS) exchanges sodium for potassium, calcium polystyrene sulfonate (CPS) has the advantage of avoiding hypervolemia because it exchanges calcium for potassium. SPS was first introduced in the 1950s and used for a long time in western countries, and CPS is currently prescribed in Asia including South Korea. In contrast with the paucity of clinical studies using SPS or CPS, the recent randomized, controlled trials reported that two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), effectively and safely reduce serum potassium levels in CKD patients taking RAAS blockades. Our experiences showed that the long-term administration of a small dose of CPS was also effective and safe in treatment of chronic hyperkalemia. Further comparative trials among patiromer, ZS-9, and CPS are required to provide guides to cost-effective management of hyperkalemia in CKD patients.