Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia

Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or downtitration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.