Hyperkalemia Causes and Risk Factors

Definition and Classification

The European Society of Cardiology defines hyperkalemia as a serum potassium concentration greater than 5 mmol/L (or 5 mEq/L) 1
Hyperkalemia can be classified as mild: >5.0 to <5.5 mEq/L 2, moderate: 5.5 to 6.0 mEq/L 3, and severe: >6.0 mEq/L 1, 3

Renal Insufficiency: The incidence of hyperkalemia increases with the severity of renal impairment, particularly when the eGFR is less than 15 mL/min/1.73 m² 3
Medications: The use of medications such as spironolactone 1, aliskiren 4, 2, and anti-inflammatory drugs 3 can increase the risk of hyperkalemia
Dietary Factors: Consuming foods rich in potassium, such as fruits (bananas, melons, orange juice) 5, and vegetables 4, can contribute to hyperkalemia
Blood Products: The use of stored blood products can also increase the risk of hyperkalemia 2

Patients with Advanced Chronic Kidney Disease: Up to 73% of patients with advanced chronic kidney disease are at risk of developing hyperkalemia 1
Patients with Chronic Heart Failure: Up to 40% of patients with chronic heart failure are at risk of developing hyperkalemia 1
Diabetic Patients: Diabetic patients are at increased risk of developing hyperkalemia 3
Elderly Patients: Elderly patients are also at increased risk of developing hyperkalemia 3

Initial Moderate to Severe Hyperkalemia: Patients with initial moderate to severe hyperkalemia (>5.6 mEq/L) are at increased risk of recurrent hyperkalemia 3
Low eGFR: Patients with a low eGFR (<45 mL/min/1.73 m²) are at increased risk of recurrent hyperkalemia 3
Diabetes: Diabetic patients are at increased risk of recurrent hyperkalemia 3
Use of Spironolactone: Patients taking spironolactone are at increased risk of recurrent hyperkalemia 3

The European Society of Cardiology notes that up to one-third of heart failure patients starting a mineralocorticoid receptor antagonist (MRA) develop hyperkalemia (>5.0 mEq/L) over 2 years 6
In real-world settings, the incidence of hyperkalemia can reach 50% in unselected populations receiving RAAS inhibitors, far exceeding the 6-12% seen in controlled clinical trials 6
Hyperkalaemia is frequently under-monitored in patients treated with RAAS inhibitors despite guideline recommendations, with 50% of cardiovascular disease patients with chronic kidney disease experiencing two or more recurrences within 1 year 6

The European Heart Journal recommends that clinicians should not discontinue or reduce RAAS inhibitors after a single elevated potassium measurement, as this offsets the survival benefits of these medications, and less than one-third of patients achieve guideline-recommended target doses 6

Potassium-sparing diuretics, such as amiloride and triamterene, impair renal potassium excretion, according to the American Journal of Kidney Diseases 7
NSAIDs impair renal potassium excretion through prostaglandin inhibition, as reported in the American Journal of Kidney Diseases 7
Calcium channel blockers can cause hyperkalemia, as noted in the American Journal of Kidney Diseases 7

High potassium intake from fruits, such as bananas and melons, can contribute to hyperkalemia, as stated in the American Journal of Kidney Diseases 7
Vegetables like potatoes and tomato products, as well as dairy products like yogurt, can also increase potassium intake, according to the American Journal of Kidney Diseases 7
Other sources, including chocolate and salt substitutes containing potassium chloride, can contribute to hyperkalemia, as reported in the American Journal of Kidney Diseases 7
Breast milk has a lower potassium content compared to standard infant formulas, but excessive volumes can still aggravate hyperkalemia in infants, as noted in the American Journal of Kidney Diseases 7

Rapid tumor cell destruction can release massive amounts of intracellular potassium into the bloodstream, leading to hyperkalemia, as described in the Journal of Clinical Oncology 8
This can occur within 12-72 hours after initiating chemotherapy, radiation, or cytolytic antibody therapy, and is most common in malignancies with high proliferative rates, according to the Journal of Clinical Oncology 8
Tumor lysis syndrome can cause life-threatening cardiac arrhythmias, ventricular tachycardia, fibrillation, or cardiac arrest, as reported in the Journal of Clinical Oncology 8