Polysulfonate Resins in Hyperkalemia: A Systematic Review

Abstract

Background: Hyperkalemia is a potentially life-threatening electrolyte abnormality defined as a serum potassium above the lab reference range (usually >5.0-5.5 mEq/L). Polystyrene resins, including sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CPS), have long been used to treat hyperkalemia. Sodium polystyrene sulfonate/calcium polystyrene sulfonate act by exchanging a cation for potassium within the intestinal lumen. While SPS and CPS have been available since the 1960s, there are rising concerns about the validity of the data supporting its use and about serious adverse gastrointestinal effects. Objective: The objective of this systematic review was to quantify the efficacy and safety of polystyrene sulfonate resins (SPS/CPS) in the treatment of adults with hyperkalemia. This review focuses on the randomized control trial (RCT), interventional non-RCT, and observational data available on SPS/CPS use. Design: Systematic review. Setting: Any country of origin. Both inpatient and outpatient settings. Patients: Adults with hyperkalemia treated with polystyrene sulfonate resins. Measurements: The primary outcome was change in serum potassium. The secondary outcomes included adverse effects of SPS/CPS and prevention of recurrent hyperkalemia. Methods: We conducted a systematic review using Cochrane Library, EMBASE (1947-2019), and Medline (1946-2019) databases. Literature reviews, systematic reviews, case studies, case series, and editorial pieces were excluded. Included studies were assessed for risk of bias. Results: Four RCTs, 21 observational studies, and 5 quasi-experimental trials were included. A total of 212 351 patients were included. Two thousand and fifty-eight patients were studied for the primary outcome and 210 293 patients were studied for the secondary outcomes. Study designs were heterogeneous and not amenable to meta-analysis. Most studies included nonhemodialysis outpatients older than 65 years. Of the included studies, 22/25 (88%) demonstrated a reduction of serum potassium >0.5 mEq/L over the study period. The magnitude of reduction in serum potassium of potassium resin compared with placebo or matched controls in the 3 low-risk studies identified was 0.14 to 1.04 mEq/L. However, each study used different dosing regimens. Ten of 22 studies reported the effects of polystyrene resins on serum potassium within 24 hours. A few high-quality observational studies suggest an increased risk of serious adverse gastrointestinal events with a relative risk of 2.10 and a hazard ratio of 1.25 to 1.94; however, the absolute risk remains low. The incidence of adverse gastrointestinal events is 16 to 23 events per 1000 person-years. Limitations: We acknowledge several limitations in this study. Case studies and case series were excluded from the search results. Large case series may have been excluded despite having comparable sample sizes to studies included due to lack of a comparator and calculated estimates. Due to the heterogeneity of the studies, the data were unable to be meta-analyzed and as such the potassium-lowering effect of polystyrene sulfonate resins remains founded on small studies with potential confounders. Conclusions: This systematic review demonstrates a continued lack of high-quality evidence for the use of SPS/CPS in hyperkalemia. Studies investigated highly variable timelines and the most robust evidence for SPS/CPS use is in chronic hyperkalemia. While the absence of high-quality evidence does not exclude the possibility of benefit, prescribers must understand that the use of SPS/CPS in acute hyperkalemia is not supported by high-quality evidence. Trial registration: The protocol for this systematic review was not registered.