Hyperkalemia in patients with chronic kidney disease (CKD) remains a challenging condition to treat, but two new oral potassium-exchanging compounds may provide clinicians with more effective therapeutic options, according to researchers.

Importantly, the investigators noted, the new agents, patiromer and sodium zirconium cyclosilicate, could enable continued use of medications that inhibit the renin-angiotensin-aldosterone system (RAAS), which interfere with potassium homeostasis. One of the most complicated issues in CKD patient management is balancing the beneficial effects of RAAS inhibitors on the cardiovascular system and kidneys with the increased risk of hyperkalemia, a team led by George L. Bakris, MD, of the University of Chicago, wrote in Expert Opinion on Pharmacotherapy (2015;published online ahead of print).

Today, therapeutic options are limited to dietary potassium restriction, correction of metabolic acidosis using bicarbonate solutions, administration of cation exchange resins to bind potassium in the large intestines, and increasing the doses of loop diuretics to enhance potassium secretion by the kidneys.

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The only currently available potassium binder in every-day clinical practice is sodium polystyrene sulfonate, a resin that exchanges 1 mEq of potassium to 1 or 2 mEq of sodium in the in the large intestines, Dr. Bakris’ group observed. The authors noted that long-term administration of this compound is problematic and linked to serious adverse effects, especially involving the gastrointestinal (GI) tract.

In recent randomized clinical trials, patiromer and sodium zirconium cyclosilicate effectively normalized elevated serum potassium levels and maintained potassium homeostasis in hyperkalemic patients treated with RAAS inhibitors. The drugs were well tolerated and were not associated with serious adverse events.

These trials compared patiromer and sodium zirconium cyclosilicate with placebo and not sodium polystyrene sulfonate, so the comparative effectiveness of the new agents and existing potassium binders for managing hyperkalemia is not known, Dr. Bakris and his collaborators stated. They pointed out that sodium polystyrene sulfonate has been associated with an increased likelihood of colonic necrosis, which is a potentially life-threatening adverse event, and other GI complications, making the drug an unsuitable comparator due to serious safety issues.

The incidence of hyperkalemia in large-scaled outcome trials involving patients with stage 3 or higher CKD who were treated with RAAS inhibitor monotherapy generally is reported to be less than 3%, the authors stated. Initiation of RAAS inhibition in these studies was largely associated with a mean serum potassium rise of 0.4–0.6 mmol/L. They pointed out, however, that these data reflect hyperkalemia recorded in clinical trials, a setting with strict enrollment criteria and monitoring of patients during follow-up visits is very close. “Thus, these low rates of hyperkalemia could substantially underestimate the true frequency of hyperkalemia associated with the use of RAAS blockers in daily clinical practice, which has been reported to be as high as 10%.”