Steroidal or non-steroidal MRAs: should we still enable RAASi use through K binders?

Abstract

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits.