What are all the causes of hyperkalemia?

Causes of Hyperkalemia

Hyperkalemia (serum potassium >5.0 mmol/L) develops due to increased potassium intake, reduced potassium excretion, or shift of potassium from intracellular to extracellular space. 1 Understanding these mechanisms is essential for proper diagnosis and management of this potentially life-threatening electrolyte disorder.

Pathophysiological Mechanisms

1. Decreased Renal Potassium Excretion

• Renal Dysfunction

  • Chronic kidney disease (CKD), especially when eGFR <15 mL/min per 1.73 m² 1
  • Acute kidney injury/acute renal failure
  • Hyporeninemic hypoaldosteronism (Type 4 renal tubular acidosis)
  • Renal tubular disorders

• Medication-Induced Impaired Excretion 1, 2, 3

  • Renin-angiotensin-aldosterone system inhibitors (RAASi):
    • ACE inhibitors (e.g., lisinopril)
    • Angiotensin receptor blockers (e.g., losartan)
    • Direct renin inhibitors (aliskiren)
    • Mineralocorticoid receptor antagonists (e.g., spironolactone)
  • Potassium-sparing diuretics (e.g., amiloride, triamterene)
  • NSAIDs
  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Trimethoprim-sulfamethoxazole
  • Heparin
  • Pentamidine
  • Beta-blockers
  • Digitalis
  • Mannitol
  • Penicillin G

2. Transcellular Potassium Shift (from intracellular to extracellular space)

• Metabolic acidosis
• Insulin deficiency/hyperglycemia 1
• Tissue breakdown:
  • Rhabdomyolysis
  • Tumor lysis syndrome
  • Hemolysis
  • Severe catabolism
• Medications affecting cellular potassium distribution:
  • Amino acids (aminocaproic acid, arginine, lysine)
  • Beta-blockers
  • Calcium channel blockers
  • Suxamethonium
  • Digoxin toxicity

3. Increased Potassium Intake/Administration 1

• Potassium supplements
• Salt substitutes (e.g., DASH diet components)
• High-potassium foods:
  • Fruits (bananas, melons, orange juice)
  • Vegetables
• Herbal supplements:
  • Alfalfa
  • Dandelion
  • Dried toad skin
  • Hawthorne berry
  • Horsetail
  • Lily of the valley
  • Milkweed
  • Nettle
  • Noni juice
  • Siberian ginseng
• Stored blood products (particularly older units)

4. Pseudo-hyperkalemia 1

• Hemolysis during blood collection
• Thrombocytosis
• Leukocytosis
• Prolonged tourniquet use
• Fist clenching during blood draw

Risk Factors for Hyperkalemia

Certain populations have increased risk for developing hyperkalemia 1:

• Advanced stages of CKD (risk increases as eGFR decreases)
• Heart failure
• Resistant hypertension
• Diabetes mellitus
• Recent myocardial infarction
• Advanced age
• Male sex
• Combination of multiple risk factors or medications

Clinical Implications

Hyperkalemia can lead to:

• Cardiac arrhythmias and cardiac arrest 4
• Neuromuscular dysfunction
• Increased hospitalization rates
• Increased mortality

Prevention Considerations

For patients at high risk of hyperkalemia:

• Regular potassium monitoring, especially when starting or increasing doses of RAASi medications
• Consider potassium binders in patients requiring RAASi therapy who develop hyperkalemia
• Dietary counseling regarding potassium intake
• Careful medication reconciliation to avoid combinations that increase hyperkalemia risk

Understanding these causes and mechanisms is critical for early detection, proper management, and prevention of potentially life-threatening complications of hyperkalemia.