What are the causes of hyperkalemia?

Causes of Hyperkalemia

The most common causes of hyperkalemia are renal failure, medication effects (particularly renin-angiotensin-aldosterone system inhibitors), and cellular release of potassium, which can lead to potentially lethal cardiac arrhythmias and cardiac arrest. 1

Pathophysiological Classification of Hyperkalemia Causes

1. Decreased Potassium Excretion

• Renal Failure

  • Acute kidney injury 1
  • Chronic kidney disease (risk increases as eGFR decreases, particularly <60 mL/min/1.73m²) 1

• Medication-Induced 1, 2

  • Renin-angiotensin-aldosterone system inhibitors (RAASi):
    • ACE inhibitors
    • Angiotensin receptor blockers (ARBs)
    • Direct renin inhibitors (aliskiren)
    • Mineralocorticoid receptor antagonists (spironolactone, eplerenone)
  • Potassium-sparing diuretics (triamterene, amiloride)
  • NSAIDs
  • Beta-blockers
  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Heparin and low molecular weight heparins
  • Trimethoprim-sulfamethoxazole
  • Pentamidine
  • Digitalis

• Hypoaldosteronism 3

  • Primary adrenal insufficiency
  • Hyporeninemic hypoaldosteronism (common in diabetic nephropathy)

2. Transcellular Shift (Movement from Intracellular to Extracellular Space)

• Acidosis - causes potassium to move out of cells 3
• Insulin deficiency - reduces cellular potassium uptake 1
• Tissue breakdown
  • Rhabdomyolysis
  • Tumor lysis syndrome
  • Hemolysis
  • Severe burns
  • Trauma
• Medications causing cellular shift 2
  • Suxamethonium (depolarizing muscle relaxant)
  • Beta-blockers (non-selective)
  • Digoxin toxicity
  • Mannitol

3. Excessive Potassium Intake/Administration

• Iatrogenic
  • IV potassium administration (especially in renal insufficiency) 1
  • Stored blood products transfusion 1
• Dietary
  • Potassium supplements 4
  • Salt substitutes 1
  • High potassium foods (bananas, melons, orange juice) in patients with impaired excretion 1
• Herbal/Alternative Products 1
  • Alfalfa
  • Dandelion
  • Hawthorne berry
  • Noni juice
  • Siberian ginseng

4. Pseudohyperkalemia

• Hemolysis during blood collection 1
• Thrombocytosis (>1,000/μL)
• Leukocytosis (>100,000/μL)
• Prolonged tourniquet use
• Fist clenching during blood draw

High-Risk Populations

Certain patient populations have increased risk for hyperkalemia 1:

• Advanced CKD (especially eGFR <15 mL/min/1.73m²)
• Heart failure
• Diabetes mellitus
• Advanced age
• Resistant hypertension
• Recent myocardial infarction
• Combination of the above conditions

Clinical Manifestations

Hyperkalemia may cause 1, 5:

• Cardiac conduction abnormalities (peaked T waves, flattened P waves, widened QRS)
• Muscle weakness
• Flaccid paralysis
• Paresthesias
• Depressed deep tendon reflexes
• Respiratory difficulties

Management Considerations

For severe hyperkalemia (>6.5 mmol/L) or with ECG changes, immediate treatment is required 1:

1. Stabilize myocardial membrane: Calcium chloride or calcium gluconate
2. Shift potassium into cells: Insulin with glucose, albuterol, sodium bicarbonate
3. Enhance potassium elimination: Loop diuretics, potassium binders, dialysis

When hyperkalemia is medication-induced, consider dose adjustment or medication alternatives rather than complete discontinuation, especially with beneficial medications like RAASi 1.

Prevention Strategies

In high-risk patients:

• Regular monitoring of serum potassium levels 1
• Dietary counseling on potassium intake 5
• Careful medication selection and dosing
• Consider newer potassium binders (patiromer, sodium zirconium cyclosilicate) for chronic management in patients requiring RAASi therapy 1, 5