Efficacy and safety of potassium binders in the treatment of patients with chronic kidney disease and hyperkalemia

Background: Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and sodium zirconium cyclosilicate (SZC), are emerging medications for the treatment of hyperkalemia with chronic kidney disease (CKD). However, which might be the best alternative for patients with chronic kidney disease and hyperkalemia remains disputed. Methods: We performed this systematic review and network meta-analysis with the Bayesian approach to conduct direct and indirect comparisons among potassium binders regarding their efficacy and safety. The surface under the cumulative ranking curve analysis (SUCRA) was used to calculate the best intervention for each outcome. Results: All four potassium binders had a promising effect regarding potassium reduction. SPS had favorable efficacy and safety for short-term use (MD:-0.94; 95% CIs:-1.4 to-0.48; SUCRA = 94.69%), but long-term treatment required strict dose control and assessment of gastrointestinal conditions. CPS had a positive effect on reducing potassium, and could especially maintain the serum potassium concentration in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Patiromer might reduce all-cause mortality in CKD patients with hyperkalemia and have a positive effect on potassium-lowering, though it had significant gastro-intestinal adverse effects. SZC had a potassium-lowering effect in both the short-term and long-term, and can be a promising long-term treatment for the hyperkalemia in CKD patients, especially in combination with RAASi. Conclusion: These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.