Sodium Polystyrene Sulfonate for Hyperkalemia

Abstract

Sodium polystyrene sulfonate (sold under the brand names SPS, Kayexalate, and Kionex) is widely used for treatment of hyperkalemia. It is a synthetic cation-bound resin that exchanges sodium cations for potassium in the gastrointestinal (GI) lumen, resulting in increased fecal potassium excretion that in turn leads to decreased serum potassium levels. This drug was first introduced for treatment of hyperkalemia in 2 small uncontrolled case series in the early 1950s, and the US Food and Drug Administration (FDA) approved it for the short-term treatment of hyperkalemia in 1958.Despite its long history of use, there have been no robust randomized clinical trials documenting the efficacy and safety of sodium polystyrene sulfonate for long-term management of hyperkalemia. Uncontrolled observational studies and 1 small randomized clinical trial demonstrated small decreases in serum potassium levels of questionable clinical significance in patients with chronic kidney disease. [1][2][3][4] No study, to our knowledge, has addressed the association of sodium polystyrene sulfonate with clinical outcomes potentially related to hyperkalemia, such as cardiac arrhythmias.In addition to very weak evidence for positive outcomes, there is mounting evidence of harm caused by this drug. Cases of intestinal necrosis associated with sodium polystyrene sulfonate in sorbitol, the typical method of administration, were reported as early as the 1980s. 5 In 2009, the FDA warned of the risk of intestinal necrosis with administration of sodium polystyrene sulfonate in sorbitol and recommended avoiding the combination of these medications in postoperative patients and those with intestinal obstruction or chronic bowel disease, including constipation. 6 The mechanism of action was thought to be related to hyperosmotic load from sorbitol leading to adenosine triphosphate-dependent sodiumpotassium pump dysfunction, alteration of cellular membrane transport systems, and reduced intestinal blood flow. 5 Comorbidities such as intestinal obstruction, diabetes, or vascular disease were also thought to contribute. In a literature review published in 2010, 7 intestinal necrosis was described only as a complication of the combination of sodium polystyrene sulfonate and sorbitol; in particular, 70% sorbitol and sodium polystyrene sulfonate preparations without sorbitol were reported to be safe. More recently, however, case reports of intestinal necrosis following sodium polystyrene sulfonate administration without sorbitol have also emerged. 8 A systematic review of 48 cases of intestinal necrosis after drug administration found 17 cases among patients not taking sorbitol, suggesting that sodium polystyrene sulfonate alone could also cause this complication. 8

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…234 After release of these findings, some have strongly recommended that SPS no longer be used. 235 Although these analyses are not randomized and residual confounding cannot be excluded, the small absolute rates (7-10 per 10,000) mean that randomized evidence to exclude or confirm these concerns is unlikely; similarly, parallel data from large-scale postmarketing studies for the newer agents will not be available for some time. We suggest the evidence priorities should be to definitively establish the benefit of potassium control for clinically meaningful events through randomized trials in order to inform assessments of risk tolerance to rare but serious events.…”

Clinical Management of Hyperkalemia

“…78 Its use varies widely among countries, ranging from 42% of patients in France to less than 1% in the United Kingdom, Spain, and Japan. 99 Sodium polystyrene sulfonate has been associated with adverse events (AEs), including intestinal ischemia and colonic necrosis, 100,101 a doubling in the risk of hospitalization for serious gastrointestinal AEs, 102 and a reported overall mortality rate of 33% for patients with serious gastrointestinal injury. 103 However, although cohort studies have reported a higher relative risk of gastrointestinal AEs with SPS use, the incidence of events with SPS was rare (16 or 23 events per 1000 person-years).…”

The dietary management of potassium in children with CKD stages 2–5 and on dialysis—clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

“…Sodium (or calcium) polystyrene sulfonate [ 69 , 70 ], although highly effective at lowering serum K + , carries a high risk of causing severe constipation, bowel necrosis, and is poorly tolerated and rarely used for the long-term management of hyperkalemia [ 72 ]. Management of hypokalemia in children with CKD2–5D Severe, life-threatening hypokalemia requires prompt medical intervention, usually requiring intravenous potassium infusion (X strong).…”

“…Sodium (or calcium) polystyrene sulfonate [69,70], although highly effective at lowering serum K + , carries a high risk of causing severe constipation, bowel necrosis, and is poorly tolerated and rarely used for the long-term management of hyperkalemia [72].…”