Hyperkalemia Risk Factors and Associated Conditions

Primary Disease States

Patients with chronic kidney disease (CKD) are at high risk of developing hyperkalemia, with up to 73% of those with advanced CKD at risk, and the incidence increases dramatically with severity of renal impairment, particularly when eGFR falls below 15 mL/min/1.73 m² 1
The American Heart Association notes that up to 40% of patients with chronic heart failure are at risk of developing hyperkalemia 1
In heart failure with reduced ejection fraction (HFrEF), up to one-third of patients starting mineralocorticoid receptor antagonists (MRAs) develop hyperkalemia (>5.0 mEq/L) over 2 years, according to the European Society of Cardiology 2, 1

The European Society of Cardiology recommends that ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (spironolactone, eplerenone) be used with caution as they are the most important medication-related causes of hyperkalemia 2, 1
Patients with cardiovascular disease and CKD on RAAS inhibitors have 50% experiencing two or more recurrences of hyperkalemia within 1 year, highlighting the need for close monitoring 1

Metabolic acidosis causes transcellular shifts of potassium from intracellular to extracellular space, increasing the risk of hyperkalemia, as noted by the European Society of Cardiology 2, 3
Tumor lysis syndrome from rapid tumor cell destruction can release massive amounts of intracellular potassium within 12-72 hours after initiating chemotherapy, radiation, or cytolytic antibody therapy, posing a high risk of hyperkalemia 1

Elderly patients are at increased risk of hyperkalemia independent of other factors, according to the American Geriatrics Society 1
Patients with initial moderate to severe hyperkalemia (>5.6 mEq/L) are at high risk of recurrent episodes, and those with low eGFR (<45 mL/min/1.73 m²) are also at increased risk of recurrence 1

The most important pitfall is discontinuing RAAS inhibitors after a single elevated potassium measurement, as this offsets the survival benefits of these medications, and instead, potassium-lowering agents should be initiated while maintaining RAAS inhibitor therapy unless severe hyperkalemia (>6.5 mEq/L) develops, as recommended by the American College of Cardiology 1, 3

Patients with chronic kidney disease have dramatically impaired potassium excretion, with up to 73% of those with advanced CKD at risk of hyperkalemia, particularly when eGFR falls below 50 mL/min is not a cited fact, however, The American Heart Association recommends monitoring potassium levels within 1 week of any medication changes, particularly when starting or escalating RAAS inhibitors, with ongoing monitoring every 3 months thereafter, for patients requiring RAAS inhibitors for cardiovascular or renal protection 4

The American College of Cardiology recommends that for patients requiring RAAS inhibitors for cardiovascular or renal protection, newer potassium binders (patiromer or sodium zirconium cyclosilicate) should be initiated rather than discontinuing life-saving medications, allowing maintenance of guideline-directed therapy while controlling potassium levels 4