Managing hyperkalemia caused by renin-angiotensin-aldosterone system inhibitors

Hyperkalemia (defined as serum potassium level ≥ 5.0 mmol/L) can lead to severe electrophysiological disturbances, including cardiac arrythmias, as well as increased morbidity and risk of death. It commonly occurs in patients with medical conditions that impair potassium excretion by the kidneys, such as in chronic kidney disease (CKD), heart failure, difficult-to-control hypertension and diabetes. These patients are often treated with renin-angiotensin-aldosterone system (RAAS) inhibitors to help reduce their risk of CKD progression and cardiovascular events. RAAS inhibitors include angiotensin-converting-enzyme inhibitors (ACEIs; e.g., lisinopril), angiotensin receptor blockers (ARBs; e.g., candesartan, valsartan), angiotensin receptor-neprilysin inhibitors (ARNIs; i.e., sacubitril-valsartan) and mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone). Some guidelines recommend up-titrating these medications to the highest approved dose that the patient can tolerate, to optimize clinical outcomes. However, these medications may trigger or exacerbate hyperkalemia, which is nearly twice as common in patients taking drugs that act on the RAAS. Read: Drop in blood pressure during surgery associated with increased risk of delirium A recent CMAJ article discusses strategies to reduce the risk of chronic hyperkalemia and optimize the care of patients being treated with RAAS inhibitors for CKD, heart failure or associated conditions. The authors note that it is challenging to try to balance the cardiorenal benefits of RAAS inhibitor treatment with the associated risk of chronic hyperkalemia. Potassium monitoring in patients on RAAS inhibitors The following frequency of potassium monitoring is suggested: Patients being considered for treatment with ACEIs or ARBs: monitor at treatment initiation; 1 to 2 weeks after initiation; 1 to 4 weeks after final dose titration; then at regular intervals based on the patient’s individual risk. Patients being considered for treatment with mineralocorticoid receptor antagonists: monitor 1 and 2 weeks after initiating or increasing the dose; 8 and 12 weeks after initiation or increasing the dose; 6, 9 and 12 months after initiation or increasing the dose; and at regular intervals thereafter based on the patient’s individual risk. Read: Thrombolysis for stroke safe in patients with large saccular aneurysms Managing patients at risk of hyperkalemia Preventive approaches to manage patients at risk of hyperkalemia are highlighted below: Encourage patients to eat a low-potassium diet and stop using supplements containing potassium. Consider referring patients to a dietitian for guidance. Treat hypertension associated with heart failure with loop or thiazide diuretics. However, diuretics can precipitate acute kidney injury and electrolyte abnormalities, and the hypokalemic response to diuretics is reduced with low estimated glomerular filtration rate. Diuretics may not be ideal for the long-term maintenance of serum potassium levels. Use sodium bicarbonate to correct metabolic acidosis and promote urinary potassium excretion. It can reduce the risk of hyperkalemia in patients with CKD and metabolic acidosis, but may need to be stopped in patients who develop volume overload. Carefully dose RAAS inhibitors and any other medications that may elevate potassium, to balance potential benefits and risks. Overall, the benefits of RAAS inhibitors are considered to outweigh their potential harms, including hyperkalemia. Recent guidelines recommend maintaining evidence-based doses of RAAS inhibitors. Lowering the dose to reduce the likelihood of recurrent hyperkalemia should be undertaken as a last resort after attempting measures to maintain evidence-based doses of RAAS inhibitors, including the use of potassium binders. Use potassium binders (sodium polystyrene sulfonate, sodium zirconium cyclosilicate, patiromer). A table in the CMAJ article summarizes the onset of action, adverse effects and dosage of these drugs. The newer potassium binders (i.e., sodium zirconium cyclosilicate and patiromer) are generally safer, more predictable in their action and better tolerated by patients. Although questions remain on their ability to improve outcomes, treatment with the newer potassium binders may mitigate the risk of recurrent hyperkalemia by rapidly and sustainably reducing serum potassium levels and enabling more optimal care of patients with guideline-recommended doses of RAAS inhibitors. The CMAJ article includes an algorithm summarizing the strategies that can be used to mitigate the risk of hyperkalemia, based on the patient’s potassium level (5.0 to 6.0 mmol/L). Reference 1. Weinstein J, Girard LP, Lepage S, et al. Prevention and management of hyperkalemia in patients treated with renin–angiotensin–aldosterone system inhibitors. CMAJ 2021;193:E1836-41.(accessed December 7, 2021).

Managing hyperkalemia caused by renin-angiotensin-aldosterone system inhibitors

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