Potassium binders for chronic hyperkalemia in people with CKD: A cochrane review and meta-analysis

Background: Hyperkalemia is a common electrolyte abnormality in patients with chronic kidney diseases (CKD). Sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CPS) are widely used but may cause severe gastrointestinal symptoms. Patiromer and sodium zirconium cyclosilicate (ZS-9) are newer potassium binders which may cause fewer gastrointestinal side-effects. This Cochrane systematic review evaluated the benefits and harms of potassium binders for treating chronic hyperkalemia among people with CKD. Methods: We searched the Cochrane Kidney and Transplant Register of Studies for randomized controlled trials (RCTs) evaluating potassium binders for chronic hyperkalemia administered in adults and children with CKD. We categorized treatments as newer agents (patiromer or ZS-9) and older agents (SPS and CPS) in separate analyses for some outcomes. Two authors independently screened citations for eligibility, extracted data, and assessed risk of bias using the Cochrane tool. Evidence certainty was evaluated using GRADE. Results: Twelve studies (1340 participants) were eligible. Medial trial duration was 3.5 weeks (range 12 hours to 52 weeks). There were no trials that evaluated treatment in children. Mean study age ranged from 53 to 73 years. Risks of bias were generally high or uncertain. Seven studies (774 participants) compared a potassium binder to placebo. Patiromer or ZS-9 had uncertain effects on all-cause mortality (relative risk [RR] 0.32, 95% CI 0.01, 7.57). The treatment effect of older potassium binders on all-cause mortality was very unclear, and no study reported outcome data for cardiovascular mortality. Potassium binders had uncertain risks of nausea (RR 2.10, 95% CI 0.65, 6.78), vomiting (RR 1.72, 95% CI 0.35, 8.51), diarrhea (RR 1.03, 95% CI 0.24, 4.51), and constipation (RR 1.68, 95% CI 0.65, 4.37). Conclusions: Evidence for different potassium binders to treat chronic hyperkalemia in people with CKD is of low certainty due to serious imprecision and trial methodological limitations. This review suggests the need for a large, adequately powered trial of potassium binders versus placebo that assesses clinical outcomes such as cardiovascular mortality, cardiac arrhythmias, health-related quality of life, and major gastrointestinal symptoms.