In-Depth Review Potassium Homeostasis and Renin-Angiotensin-Aldosterone System Inhibitors

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy in treating hypertension and cardiovascular and renal diseases. However, RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors) increase the risk of hyperkalemia (serum potassium >5.5 mmol/L). This review evaluates the effects on serum potassium levels of RAAS inhibitors. Using PubMed, we searched for clinical trials published up to December 2008 assessing the effects on serum potassium levels of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors, alone and in combination, in patients with hypertension, heart failure (HF), or chronic kidney disease (CKD); 39 studies were identified. In patients with hypertension without risk factors for hyperkalemia, the incidence of hyperkalemia with RAAS inhibitor monotherapy is low (<2%), whereas rates are higher with dual RAAS inhibition ( 5%). The incidence of hyperkalemia is also increased in patients with HF or CKD (5% to 10%). However, increases in serum potassium levels are small ( 0.1 to 0.3 mmol/L), and rates of study discontinuation due to hyperkalemia are low, even in high-risk patient groups (1% to 5%). Patients with HF or CKD are at greater risk of hyperkalemia with RAAS inhibitors than those without these conditions. However, the absolute changes in serum potassium are generally small and unlikely to be clinically significant. Moreover, these patients are likely to derive benefit from RAAS inhibition. Rather than denying them an effective treatment, electrolyte levels should be closely monitored in these patients. Clin J Am Soc Nephrol 5: 531–548, 2010. doi: 10.2215/CJN.07821109