What are the causes and management strategies for hyperkalemia?

Causes of Persistently Elevated Potassium

The main causes of persistently elevated potassium (hyperkalemia) include chronic kidney disease, heart failure, diabetes, medication effects (particularly RAAS inhibitors), and excessive potassium intake, with management requiring identification of underlying causes and appropriate treatment based on severity. 1, 2

Risk Factors and Causes of Hyperkalemia

Major Causes:

• Decreased renal excretion:

  • Chronic kidney disease (CKD), especially with eGFR <60 mL/min/1.73 m² 1
  • Acute kidney injury
  • End-stage renal disease
  • Hyporeninemic hypoaldosteronism (common in diabetic nephropathy) 3

• Medication-induced:

  • RAAS inhibitors (ACE inhibitors, ARBs)
  • Potassium-sparing diuretics (spironolactone)
  • NSAIDs
  • Beta-blockers
  • Calcineurin inhibitors
  • Heparin and derivatives
  • Trimethoprim, pentamidine 1, 2

• Transcellular shifts:

  • Acidosis
  • Hyperglycemia
  • Cell lysis (rhabdomyolysis, tumor lysis syndrome)
  • Insulin deficiency 4

• Other causes:

  • Excessive potassium intake (dietary or supplements)
  • Adrenal insufficiency
  • Advanced age 1

Risk Stratification:

• Risk increases progressively as eGFR decreases, particularly when <15 mL/min/1.73 m² 1
• Higher risk in patients with:
  • Advanced CKD
  • Heart failure
  • Resistant hypertension
  • Diabetes
  • Myocardial infarction
  • Combinations of these conditions 1

Management of Hyperkalemia

Assessment of Severity:

• Mild: K+ 5.0-5.5 mEq/L
• Moderate: K+ 5.6-6.0 mEq/L
• Severe: K+ >6.0 mEq/L 1, 2

Acute Management (K+ >6.0 mEq/L or symptomatic):

1. Cardiac membrane stabilization (immediate effect, 1-3 minutes):

   • IV calcium (10 mL of 10% calcium gluconate) 1, 2

2. Intracellular potassium shift (15-60 minutes):

   • IV insulin (10 units) with glucose (50 mL of 25% dextrose)
   • Nebulized beta-agonists (10-20 mg salbutamol)
   • IV sodium bicarbonate (only in patients with metabolic acidosis) 1, 2

3. Potassium elimination:

   • Loop diuretics (in non-oliguric patients)
   • Hemodialysis (for severe, resistant hyperkalemia or in patients with oliguria/anuria or ESRD) 1, 2

Chronic Management:

1. Identify and address underlying causes:

   • Modify medication regimens when possible
   • Treat underlying conditions 2

2. Potassium binders:

   • Newer agents (patiromer or sodium zirconium cyclosilicate) are preferred for long-term management 2
   • Sodium polystyrene sulfonate is an alternative but should not be used for emergency treatment due to delayed onset of action 2, 5

3. Dietary modifications:

   • Low-potassium diet, though evidence supporting direct link between dietary potassium and serum levels is limited 1, 2

4. Monitoring:

   • Repeat serum potassium within 1 week of treatment initiation
   • More frequent monitoring in high-risk patients (CKD, heart failure, diabetes) 2

Special Considerations

RAAS Inhibitor Management:

• For K+ 4.5-5.0 mmol/L: Continue/initiate RAAS inhibitors with close monitoring
• For K+ >5.0-<6.5 mmol/L: Consider potassium binders while maintaining RAAS inhibitors if possible
• For K+ >6.5 mmol/L: Discontinue/reduce RAAS inhibitors temporarily 2

Common Pitfalls to Avoid:

• Pseudohyperkalemia: Always verify elevated potassium with a repeat sample to rule out hemolysis during phlebotomy 2
• Overtreatment: Monitor for rebound hypokalemia, especially with aggressive treatment 2
• Undertreatment: Failure to recognize and treat hyperkalemia can lead to life-threatening arrhythmias 6
• Medication interactions: Be aware of medications that can worsen hyperkalemia when used in combination 1, 2

Indications for Urgent Treatment:

• Severe hyperkalemia (K+ >6.5 mEq/L)
• Presence of ECG changes (peaked T waves, widened QRS, prolonged PR interval)
• Symptomatic hyperkalemia (muscle weakness, paralysis)
• Rapid rise in serum potassium 2, 6

By systematically addressing the underlying causes and implementing appropriate treatment strategies based on severity, persistently elevated potassium can be effectively managed to reduce associated morbidity and mortality.