Most of the regulation of renal potassium excretion occurs in the aldosterone sensitive distal nephron (ASDN). Two principal determinants of potassium secretion in ASDN are mineralocorticoid activity and distal delivery of sodium and water. In patients with CKD, loss of nephron mass is counterbalanced by an adaptive increase in the secretory rate of potassium in remaining nephrons such that potassium homeostasis is generally well-maintained until the GFR falls below 15-20 mL/min. The incidence and prevalence of hyperkalemia in the general population is low. CKD patients are at higher risk for hyperkalemia, especially those who are treated with RAAS inhibitors (RAASi).

Hyperkalemia is one of the main reasons why these drugs have to be discontinued in many patients with CKD, in spite of their beneficial effects. Ideal approach is to control hyperkalemia without discontinuation of these drugs. Currently available oral anti-hyperkalemic agents, like diuretics and sodium or calcium polystyrene sulfonate, have poor efficacy or safety to use over long-term in combination with RAASi.

Novel potassium binding agents like patiromer and sodium zirconium cyclosilicate may enable continuation of RAASi in patients with CKD, effectively manage hyperkalemia on a long-term basis and have a favorable side effect profile.