Causes of Hyperkalemia (Elevated Potassium)
Hyperkalemia, defined as serum potassium >5.0 mmol/L, is primarily caused by impaired renal excretion, excessive intake, or shift of potassium from intracellular to extracellular space. 1
Major Causes of Hyperkalemia
Decreased Renal Excretion
- Chronic kidney disease (CKD), especially when eGFR <15 mL/min/1.73 m², is a primary cause of hyperkalemia due to reduced potassium filtration 1
- Acute kidney injury or acute renal failure 2
- Hypoaldosteronism (reduced aldosterone effect) 2
- Urinary obstruction 1
Medication-Induced Hyperkalemia
- Renin-angiotensin-aldosterone system inhibitors (RAASi):
- ACE inhibitors
- Angiotensin receptor blockers (ARBs)
- Mineralocorticoid receptor antagonists (e.g., spironolactone)
- Direct renin inhibitors (aliskiren) 1
- Potassium-sparing diuretics (e.g., triamterene, amiloride) 1
- NSAIDs (non-steroidal anti-inflammatory drugs) 1
- Beta-blockers 1, 3
- Calcineurin inhibitors (cyclosporine, tacrolimus) 1
- Heparin and derivatives 1, 3
- Trimethoprim-sulfamethoxazole 1
- Pentamidine 1
- Digitalis 1
- Mannitol 1
- Sacubitril/valsartan 1
- Penicillin G (in high doses) 1
Increased Potassium Intake
- Excessive dietary potassium consumption 1
- Potassium supplements 1
- Salt substitutes containing potassium chloride 1, 4
- Stored blood products (due to release of potassium from cells during storage) 1
- High-potassium foods (bananas, oranges, potatoes, tomatoes, legumes) 1
- Nutritional supplements, including muscle-building supplements 4
Transcellular Shifts (Movement from Intracellular to Extracellular Space)
- Acidosis (causes potassium to move out of cells) 1
- Rhabdomyolysis (muscle breakdown releasing intracellular potassium) 1, 2
- Hemolysis (red blood cell destruction, e.g., from blood transfusions) 1
- Tumor lysis syndrome (rapid breakdown of malignant cells) 1
- Insulin deficiency or resistance 3
- Severe hyperglycemia 5
- Medications that alter transmembrane potassium movement:
- Suxamethonium
- Amino acids
- Calcium channel blockers 3
Risk Factors for Hyperkalemia
- Advanced CKD (especially eGFR <45 mL/min/1.73 m²) 1
- Diabetes mellitus 1
- Heart failure 1
- Advanced age 1
- Combination of multiple potassium-altering medications 1
- Male gender (slightly higher risk) 1
Clinical Significance
- Hyperkalemia can cause cardiac arrhythmias, ventricular fibrillation, and sudden cardiac death 1
- Neuromuscular symptoms include weakness, paralysis, and paresthesia 1, 4
- Gastrointestinal symptoms may include nausea, vomiting, and ileus 4
- Severity classification:
- Mild: >5.0 to <5.5 mEq/L
- Moderate: 5.5 to 6.0 mEq/L
- Severe: >6.0 mEq/L 1
Common Pitfalls
- Failing to recognize pseudo-hyperkalemia (falsely elevated potassium due to hemolysis during blood collection) 1
- Overlooking medication-induced causes, especially in patients with multiple comorbidities 3
- Inadequate monitoring of high-risk patients on RAASi therapy 1
- Underestimating the risk of hyperkalemia in patients with mild to moderate CKD 1
- Failing to consider nutritional supplements and salt substitutes as potential sources of excessive potassium 4
Understanding these causes is essential for proper diagnosis, prevention, and management of hyperkalemia, particularly in high-risk populations with reduced renal function or those taking medications that affect potassium homeostasis.